RESUMEN

Acinetobacter baumannii emerged as one of the most important pathogens for the development of new antimicrobials due to the worldwide detection of isolates resistant to all commercial antibiotics, especially in nosocomial infections. Biofilm formation enhances A. baumannii survival by impairing antimicrobial action, being an important target for new antimicrobials. Fluopsin C (FlpC) is an organocupric secondary metabolite with broad-spectrum antimicrobial activity. This study aimed to evaluate the antibiofilm activity of FlpC in established biofilms of extensively drug-resistant A. baumannii (XDRAb) and the effects of its combination with polymyxin B (PolB) on planktonic cells. XDRAb susceptibility profiles were determined by Vitek 2 Compact, disk diffusion, and broth microdilution. FlpC and PolB interaction was assessed using the microdilution checkerboard method and time-kill kinetics. Biofilms of XDRAb characterization and removal by FlpC exposure were assessed by biomass staining with crystal violet. Confocal Laser Scanning Microscopy was used to determine the temporal removal of the biofilms using DAPI, and cell viability using live/dead staining. The minimum inhibitory concentration (MIC) of FlpC on XDRAb was 3.5 µg mL-1. Combining FlpC + PolB culminated in an additive effect, increasing bacterial susceptibility to both antibiotics. FlpC-treated 24 h biofilms reached a major biomass removal of 92.40 ± 3.38% (isolate 230) using 7.0 µg mL-1 FlpC. Biomass removal occurred significantly over time through the dispersion of the extracellular matrix and decreasing cell number and viability. This is the first report of FlpC's activity on XDRAb and the compound showed a promissory response on planktonic and sessile cells, making it a candidate for the development of a new antimicrobial product.

RESUMEN

Advanced diagnostic technologies have made accurate and precise diagnosis of pathogens easy. Herein, we present a new diagnostic method, droplet digital PCR (ddPCR), to detect and quantify Acinetobacter baumannii in mini bronchoalveolar lavage (mini-BAL) samples. A. baumannii causes ventilator-associated pneumonia (VAP), a severe healthcare infection affecting patients' lungs. VAP carries a high risk of morbidity and mortality, making its timely diagnosis crucial for prompt and effective management. Methodology. The assay performance was evaluated by comparing colonization data, quantitative culture results, and different generations of PCR (traditional PCR and Real-Time PCR-qPCR Taqman® and SYBR® Green). The ddPCR and qPCR Taqman® prove to be more sensitive than other molecular techniques. Reasonable analytical specificity was obtained with ddPCR, qPCR TaqMan®, and conventional PCR. However, qPCR SYBR® Green technology presented a low specificity, making the results questionable in clinical samples. DdPCR detected/quantified A. baumanni in more clinical samples than other methods (38.64% of the total samples). This emerging ddPCR technology offers promising advantages such as detection by more patients and direct quantification of pathogens without calibration curves.

RESUMEN

Much knowledge about bacteriophages has been obtained via genomics and metagenomics over the last decades. However, most studies dealing with prophage diversity have rarely conducted phage species delimitation (aspect 1) and have hardly integrated the population structure of the host (aspect 2). Yet, these two aspects are essential in assessing phage diversity. Here, we implemented an operational definition of phage species (clustering at 95% identity, 90% coverage) and integrated the host's population structure to understand prophage diversity better. Gathering the most extensive data set of Acinetobacter baumannii phages (4,152 prophages + 122 virulent phages, distributed in 46 countries in the world), we show that 91% (875 out of 963) of the prophage species have four or fewer prophages per species, and just five prophage species have more than 100 prophages. Most prophage species have a narrow host range and are geographically restricted; yet, very few have a broad host range being well spread in distant lineages of A. baumannii. These few broad host range prophage species are not only cosmopolitan but also the most abundant species. We also noted that polylysogens had very divergent prophages, belonging to different prophage species, and prophages can easily be gained and lost within the bacterial lineages. Finally, even with this extensive data set, the prophage diversity has not been fully grasped. Our study highlights how integrating the host population structure and a solid operational definition of phage species allows us to better appreciate phage diversity and its transmission dynamics. IMPORTANCE: Much knowledge about bacteriophages has been obtained via genomics and metagenomics over the last decades. However, most studies dealing with prophage diversity have rarely conducted phage species delimitation (aspect 1) and have hardly integrated the population structure of the host (aspect 2). Yet, these two aspects are essential in assessing phage diversity. Here, we implemented an operational definition of phage species (clustering at 95% identity, 90% coverage) and integrated the host's population structure to understand prophage diversity better. Gathering the most extensive data set of Acinetobacter baumannii phages, we show that most prophage species have four or fewer prophages per species, and just five prophage species have more than 100 prophages. Most prophage species have a narrow host range and are geographically restricted; yet, very few have a broad host range being well spread in distant lineages of A. baumannii. These few broad host range prophage species are cosmopolitan and the most abundant species. Prophages in the same bacterial genome are very divergent, and prophages can easily be gained and lost within the bacterial lineages. Finally, even with this extensive data set, the prophage diversity has not been fully grasped. This study shows how integrating the host population structure and clustering at the species level allows us to better appreciate phage diversity and its transmission dynamics.

Asunto(s)

Especificidad del Huésped , Profagos , Profagos/genética , Profagos/fisiología , Profagos/clasificación , Acinetobacter baumannii/virología , Acinetobacter baumannii/genética , Acinetobacter baumannii/clasificación , Metagenómica , Filogenia , Genoma Viral , Bacteriófagos/genética , Bacteriófagos/fisiología , Bacteriófagos/clasificación , Bacteriófagos/aislamiento & purificación

RESUMEN

Acinetobacter baumannii is a globally disseminated Gram-negative bacterium that causes several types of serious nosocomial infections, the most worrisome being ventilator-associated pneumonia and bacteremia related to using venous catheters. Due to its great ability to form biofilms, combined with its survival for prolonged periods on abiotic surfaces and its potential to acquire and control the genes that determine antibiotic resistance, A. baumannii is at the top of the World Health Organization's priority list of pathogens in urgent need of new therapies. In this sense, this review aimed to present and discuss new molecular targets present in A. baumannii with potential for promising treatment approaches. This review highlights crucial molecular targets, including cell division proteins, membrane synthesis enzymes, and biofilm-associated components, offering promising targets for novel antimicrobial drug development against A. baumannii infections.

RESUMEN

Acinetobacter baumannii es una bacteria oportunista que representa un desafío significativo en el ámbito clínico debido a su rápida diseminación, elevada mortalidad y altos niveles de resistencia a los antimicrobianos convencionales. Esto ha impulsado la búsqueda de alternativas terapéuticas eficaces para el manejo de infecciones causadas por este patógeno. Objetivo: Evaluar la actividad antibacteriana in vitro del extracto de Taraxacum officinale (diente de león) frente a cepas de Acinetobacter baumannii. Materiales y Métodos: Se utilizaron cultivos in vitro con medio Muller Hinton y agar nutritivo para la activación y propagación de la cepa de referencia A. baumannii ATCC BAA-1605. Se obtuvo un extracto etanólico de T. officinale y se evaluaron diferentes concentraciones del mismo. Resultados: El extracto de T. officinale no mostró actividad antibacteriana significativa frente a. baumannii, ya que no se observó la formación de halos de inhibición, incluyendo en la prueba con el control positivo de Ciprofloxacina. Estos hallazgos llevaron a aceptar la hipótesis nula y rechazar la hipótesis alternativa, lo que sugiere una escasa eficacia del extracto de la planta frente a esta bacteria. Conclusiones: Se resalta la necesidad de realizar investigaciones más exhaustivas para comprender mejor los mecanismos de acción y la eficacia del extracto de T. officinale, así como explorar su potencial aplicación clínica en el tratamiento de infecciones causadas por A. baumannii dado que esta bacteria presenta altos niveles de resistencia a los antimicrobianos convencionales

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Acinetobacter baumannii is an opportunistic bacteria that represents a significant challenge in the clinical field due to its rapid dissemination, high mortality, and high levels of resistance to conventional antimicrobials. This has driven the search for effective therapeutic alternatives for the management of infections caused by this pathogen. Objective: To evaluate the in vitro antibacterial activity of the Taraxacum officinale (dandelion) extract against Acinetobacter baumannii strains. Materials and Methods: In vitro cultures with Muller Hinton medium and nutrient agar were used for the activation and propagation of the reference strain A. baumannii ATCC BAA-1605. An ethanolic extract of T. officinale was obtained, and different concentrations of the extract were evaluated. Results: The T. officinale extract did not show significant antibacterial activity against A. baumannii, as no formation of inhibition halos was observed, including in the test with the positive control of Ciprofloxacin. These findings led to accepting the null hypothesis and rejecting the alternative hypothesis, suggesting a poor efficacy of the plant extract against this bacterium. Conclusions: The need to conduct more extensive research to better understand the mechanisms of action and the efficacy of the T. officinale extract is highlighted, as well as to explore its potential clinical application in the treatment of infections caused by A. baumannii, as this bacterium presents high levels of resistance to conventional antimicrobials.

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Acinetobacter baumannii é uma bactéria oportunista que representa um desafio significativo no campo clínico devido à sua rápida disseminação, elevada mortalidade e altos níveis de resistência a antimicrobianos convencionais. Isso tem impulsionado a busca por alternativas terapêuticas eficazes para o manejo de infecções causadas por esse patógeno. Objetivo: Avaliar a atividade antibacteriana in vitro do extrato de Taraxacum officinale (dente-de-leão) contra cepas de Acinetobacter baumannii. Materiais e Métodos: Culturas in vitro com meio Muller Hinton e ágar nutritivo foram utilizadas para a ativação e propagação da cepa de referência A. baumannii ATCC BAA-1605. Um extrato etanólico de T. officinale foi obtido e diferentes concentrações do extrato foram avaliadas. Resultados: O extrato de T. officinale não mostrou atividade antibacteriana significativa contra A. baumannii, uma vez que não foi observada a formação de halos de inibição, incluindo no teste com o controle positivo de Ciprofloxacina. Esses achados levaram à aceitação da hipótese nula e rejeição da hipótese alternativa, sugerindo uma eficácia limitada do extrato da planta contra essa bactéria. Conclusões: Destaca-se a necessidade de realizar pesquisas mais amplas para compreender melhor os mecanismos de ação e a eficácia do extrato de T. officinale, bem como explorar sua potencial aplicação clínica no tratamento de infecções causadas por A. baumannii, uma vez que essa bactéria apresenta altos níveis de resistência a antimicrobianos convencionais.

Asunto(s)

Taraxacum

RESUMEN

Acinetobacter baumannii es una bacteria oportunista que representa un desafío significativo en el ámbito clínico debido a su rápida diseminación, elevada mortalidad y altos niveles de resistencia a los antimicrobianos convencionales. Esto ha impulsado la búsqueda de alternativas terapéuticas eficaces para el manejo de infecciones causadas por este patógeno. Objetivo: Evaluar la actividad antibacteriana in vitro del extracto de Taraxacum officinale (diente de león) frente a cepas de Acinetobacter baumannii. Materiales y Métodos: Se utilizaron cultivos in vitro con medio Muller Hinton y agar nutritivo para la activación y propagación de la cepa de referencia A. baumannii ATCC BAA-1605. Se obtuvo un extracto etanólico de T. officinale y se evaluaron diferentes concentraciones del mismo. Resultados: El extracto de T. officinale no mostró actividad antibacteriana significativa frente a. baumannii, ya que no se observó la formación de halos de inhibición, incluyendo en la prueba con el control positivo de Ciprofloxacina. Estos hallazgos llevaron a aceptar la hipótesis nula y rechazar la hipótesis alternativa, lo que sugiere una escasa eficacia del extracto de la planta frente a esta bacteria. Conclusiones: Se resalta la necesidad de realizar investigaciones más exhaustivas para comprender mejor los mecanismos de acción y la eficacia del extracto de T. officinale, así como explorar su potencial aplicación clínica en el tratamiento de infecciones causadas por A. baumannii dado que esta bacteria presenta altos niveles de resistencia a los antimicrobianos convencionales.

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Acinetobacter baumannii is an opportunistic bacteria that represents a significant challenge in the clinical field due to its rapid dissemination, high mortality, and high levels of resistance to conventional antimicrobials. This has driven the search for effective therapeutic alternatives for the management of infections caused by this pathogen. Objective: To evaluate the in vitro antibacterial activity of the Taraxacum officinale (dandelion) extract against Acinetobacter baumannii strains. Materials and Methods: In vitro cultures with Muller Hinton medium and nutrient agar were used for the activation and propagation of the reference strain A. baumannii ATCC BAA-1605. An ethanolic extract of T. officinale was obtained, and different concentrations of the extract were evaluated. Results: The T. officinale extract did not show significant antibacterial activity against A. baumannii, as no formation of inhibition halos was observed, including in the test with the positive control of Ciprofloxacin. These findings led to accepting the null hypothesis and rejecting the alternative hypothesis, suggesting a poor efficacy of the plant extract against this bacterium. Conclusions: The need to conduct more extensive research to better understand the mechanisms of action and the efficacy of the T. officinale extract is highlighted, as well as to explore its potential clinical application in the treatment of infections caused by A. baumannii, as this bacterium presents high levels of resistance to conventional antimicrobials.

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Acinetobacter baumannii é uma bactéria oportunista que representa um desafio significativo no campo clínico devido à sua rápida disseminação, elevada mortalidade e altos níveis de resistência a antimicrobianos convencionais. Isso tem impulsionado a busca por alternativas terapêuticas eficazes para o manejo de infecções causadas por esse patógeno. Objetivo: Avaliar a atividade antibacteriana in vitro do extrato de Taraxacum officinale (dente-de-leão) contra cepas de Acinetobacter baumannii. Materiais e Métodos: Culturas in vitro com meio Muller Hinton e ágar nutritivo foram utilizadas para a ativação e propagação da cepa de referência A. baumannii ATCC BAA-1605. Um extrato etanólico de T. officinale foi obtido e diferentes concentrações do extrato foram avaliadas. Resultados: O extrato de T. officinale não mostrou atividade antibacteriana significativa contra A. baumannii, uma vez que não foi observada a formação de halos de inibição, incluindo no teste com o controle positivo de Ciprofloxacina. Esses achados levaram à aceitação da hipótese nula e rejeição da hipótese alternativa, sugerindo uma eficácia limitada do extrato da planta contra essa bactéria. Conclusões: Destaca-se a necessidade de realizar pesquisas mais amplas para compreender melhor os mecanismos de ação e a eficácia do extrato de T. officinale, bem como explorar sua potencial aplicação clínica no tratamento de infecções causadas por A. baumannii, uma vez que essa bactéria apresenta altos níveis de resistência a antimicrobianos convencionais.

RESUMEN

Staphylococcus aureus and Acinetobacter baumannii are opportunistic pathogens, and both are involved in different oral infections. This work aimed to analyze the phytochemical composition of Myrciaria cauliflora hydroethanolic extract and to evaluate its antimicrobial and antibiofilm action against Staphylococcus aureus (ATCC 6538) and Acinetobacter baumannii (ATCC 19606; multi-resistant clinical strains 58004, 50098, 566006, and H557). Myrciaria cauliflora hydroethanolic extract was prepared, and the content of soluble solids, flavonoids, and phenols was quantified. High-performance liquid chromatography (HPLC) was performed later. The minimum inhibitory concentration was determined using the broth microdilution method according to the Clinical and Laboratory Standards Institute, standard M7-A6, and subsequently, its minimum bactericidal concentration was determined. Then, the most effective concentrations were analyzed against biofilms. Statistical analysis was performed using the ANOVA method with Tukey's test. The soluble solids content in the prepared hydroethanolic extract of M. cauliflora was 2.22%. Additionally, the total flavonoid content, measured using the quercetin standard curve, was 0.040 mg/mL. Furthermore, the total phenol content, determined using the gallic acid standard curve, was 0.729 mg/mL. HPLC analysis presented peaks of gallic acid (11.80 m), p-coumaric acid (12.09 m), cinnamic acid derivative (19.02 m), and ellagic acid (29.83 m). The extract demonstrated antimicrobial and antibiofilm action against all tested strains. However, the most effective antibacterial concentration against all the tested bacteria was 5.55 mg/mL. Therefore, these chemical components justify that M. cauliflora hydroethanolic extract is effective in reducing biofilm formation in S. aureus (standard strain) and A. baumannii (standard and clinical strains).

RESUMEN

Introduction: Acinetobacter baumannii contributes significantly to the global issue of multidrug-resistant (MDR) nosocomial infections. Often, these strains demonstrate resistance to carbapenems (MDR-CRAB), the first-line treatment for infections instigated by MDR A. baumannii. Our study focused on the antimicrobial susceptibility and genomic sequences related to plasmids from 12 clinical isolates of A. baumannii that carry both the blaOXA-58 and bla NDM-1 carbapenemase genes. Methods: Whole-genome sequencing with long-read technology was employed for the characterization of an A. baumannii plasmid that harbors the bla OXA-58 and blaNDM-1 genes. The location of the bla OXA-58 and bla NDM-1 genes was confirmed through Southern blot hybridization assays. Antimicrobial susceptibility tests were conducted, and molecular characterization was performed using PCR and PFGE. Results: Multilocus Sequence Typing analysis revealed considerable genetic diversity among bla OXA-58 and bla NDM-1 positive strains in Brazil. It was confirmed that these genes were located on a plasmid larger than 300 kb in isolates from the same hospital, which also carry other antimicrobial resistance genes. Different genetic contexts were observed for the co-occurrence of these carbapenemase-encoding genes in Brazilian strains. Discussion: The propagation of bla OXA-58 and bla NDM-1 genes on the same plasmid, which also carries other resistance determinants, could potentially lead to the emergence of bacterial strains resistant to multiple classes of antimicrobials. Therefore, the characterization of these strains is of paramount importance for monitoring resistance evolution, curbing their rapid global dissemination, averting outbreaks, and optimizing therapy.

RESUMEN

Acinetobacter baumannii poses a significant health threat because of its frequent implications in hospital outbreaks and multidrug resistance (MDR). Here, we studied four A. baumannii isolates recovered during a hospital outbreak of severe or fatal cases to elucidate their diversity and factors contributing to their increased virulence and antibiotic resistance. The isolates were identified using MALDI-ToF and characterized using comparative genomics, PCR, and antimicrobial susceptibility tests. They were classified as ST126 and exhibited fewer than five chromosomal single-nucleotide variants and the same extrachromosomal content, indicating that they are a single strain (A. baumannii AB01). A. baumannii AB01 showed an MDR phenotype that could be linked to the carriage of parC and gyrA mutations, efflux transporters, aminoglycoside resistance genes, a class C beta-lactamase, and three carbapenemases, some of which are encoded on a 72 kb plasmid. ST126 is infrequent and has not been reported in Latin America, and our genomic data indicate a plausible origin for A. baumannii AB01 within the Pan Pacific region.

Asunto(s)

Infecciones por Acinetobacter , Acinetobacter baumannii , Proteínas Bacterianas , Brotes de Enfermedades , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Plásmidos , beta-Lactamasas , beta-Lactamasas/genética , Humanos , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/epidemiología , Acinetobacter baumannii/genética , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/enzimología , Acinetobacter baumannii/aislamiento & purificación , Farmacorresistencia Bacteriana Múltiple/genética , Plásmidos/genética , Proteínas Bacterianas/genética , Antibacterianos/farmacología , Masculino , Femenino , Infección Hospitalaria/microbiología , Infección Hospitalaria/epidemiología , Persona de Mediana Edad

RESUMEN

To assess the antibacterial effectiveness of Lippia macrophylla essential oil (LMEO) against multidrug-resistant Acinetobacter baumannii isolates, both as a standalone treatment and in combination with conventional antibiotics. LMEO demonstrated a significant inhibitory effect on the growth of A. baumannii, with a minimum inhibitory concentration (MIC) below 500 µg/mL. Notably, LMEO was capable of reversing the antibiotic resistance of clinical isolates or reducing their MIC values when used in combination with antibiotics, showing synergistic (FICI≤0.5) or additive effects. The combination of LMEO and imipenem was particularly effective, displaying synergistic interactions for most isolates. Ultrastructural analyses supported these findings, revealing that the combination of LMEO+ceftazidime compromised the membrane integrity of the Acb35 isolate, leading to cytoplasmic leakage and increased formation of Outer Membrane Vesicles (OMVs). Taken together our results point for the use of LMEO alone or in combination as an antibacterial agent against A. baumannii. These findings offer promising avenues for utilizing LMEO as a novel antibacterial strategy against drug-resistant infections in healthcare settings, underscoring the potential of essential oils in enhancing antibiotic efficacy.

Asunto(s)

Acinetobacter baumannii , Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Lippia , Pruebas de Sensibilidad Microbiana , Aceites Volátiles , Acinetobacter baumannii/efectos de los fármacos , Aceites Volátiles/farmacología , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificación , Lippia/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Humanos , Relación Dosis-Respuesta a Droga

RESUMEN

Acinetobacter baumannii belongs to the ESKAPE group. It is classified as a critical priority group by the World Health Organization and a global concern on account of its capacity to acquire and develop resistance mechanisms to multiple antibiotics. Data from the United States indicates 500 deaths annually. Resistance mechanisms of this bacterium include enzymatic pathways such as ß-lactamases, carbapenemases, and aminoglycoside-modifying enzymes, decreased permeability, and overexpression of efflux pumps. A. baumannii has been demonstrated to possess efflux pumps, which are classified as members of the MATE family, RND and MFS superfamilies, and SMR transporters. The aim of our work was to assess the distribution of efflux pumps and their regulatory gene expression in clinical strains of A. baumannii isolated from burned patients. METHODS: From the Clinical Microbiology Laboratory at the Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra collection in Mexico, 199 strains were selected. Antibiotics susceptibilities were performed by broth microdilutions to determine minimal inhibitory concentrations. Phenotypic assays with efflux pump inhibitors were conducted using carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and phenylalanine-arginine ß-naphthylamide (PAßN) in conjunction with amikacin, ceftazidime, imipenem, meropenem and levofloxacin. A search was conducted for structural genes that are linked to efflux pumps, and the relative expression of the adeR, adeS, and adeL genes was analyzed. RESULTS: Among a total of 199 strains, 186 exhibited multidrug resistance (MDR). Fluoroquinolones demonstrated the highest resistance rates, while minocycline and amikacin displayed comparatively reduced resistance rates (1.5 and 28.1, respectively). The efflux activity of fluorquinolones exhibited the highest phenotypic detection (from 85 to 100%), while IMP demonstrated the lowest activity of 27% with PAßN and 43.3% with CCCP. Overexpression was observed in adeS and adeL, with adeR exhibiting overexpression. Concluding that clinical strains of A. baumannii from our institution exhibited efflux pumps as one of the resistance mechanisms.

RESUMEN

Due to its antimicrobial resistance characteristics, the World Health Organization (WHO) classifies A. baumannii as one of the critical priority pathogens for the development of new therapeutic strategies. Vaccination has been approached as an interesting strategy to overcome the lack of effective antimicrobials and the long time required to develop and approve new drugs. In this study, we aimed to evaluate as a vaccine the hypothetical adhesin protein CAM87009.1 in its recombinant format (rCAM87009.1) associated with aluminum hydroxide (Alhydrogel®) or biogenic silver nanoparticles (bio-AgNP) as adjuvant components against lethal infection by A. baumannii MDR strain. Both vaccine formulations were administered in three doses intramuscularly in BALB/c murine models and the vaccinated animals were tested in a challenge assay with A. baumannii MDR strain (DL100). rCAM87009.1 protein associated with both adjuvants was able to protect 100 % of animals challenged with the lethal strain during the challenge period. After the euthanasia of the animals, no A. baumannii colonies were detected in the lungs of animals vaccinated with the rCAM87009.1 protein in both formulations. Since the first immunization, high IgG antibody titers were observed (1:819,200), with results being statistically similar in both vaccine formulations evaluated. rCAM87009.1 associated with both adjuvants was capable of inducing at least one class of isotypes associated with the processes of neutralization (IgG2b and IgA for bio-AgNP and Alhydrogel®, respectively), opsonization (IgG1 in both vaccines) and complement activation (IgM and IgG3 for bio-AgNP and Alhydrogel®, respectively). Furthermore, reduced tissue damage was observed in animals vaccinated with rCAM87009.1 + bio-AgNP when compared to animals vaccinated with Alhydrogel®. Our results indicate that the rCAM87009.1 protein associated with both bio-AgNP and Alhydrogel® are combinations capable of promoting immunity against infections caused by A. baumannii MDR. Additionally, we demonstrate the potential of silver nanoparticles as alternative adjuvant molecules to the use of aluminum salts.

Asunto(s)

Infecciones por Acinetobacter , Acinetobacter baumannii , Adhesinas Bacterianas , Adyuvantes Inmunológicos , Anticuerpos Antibacterianos , Nanopartículas del Metal , Ratones Endogámicos BALB C , Plata , Animales , Plata/administración & dosificación , Plata/farmacología , Acinetobacter baumannii/inmunología , Acinetobacter baumannii/efectos de los fármacos , Ratones , Infecciones por Acinetobacter/prevención & control , Infecciones por Acinetobacter/inmunología , Adhesinas Bacterianas/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Farmacorresistencia Bacteriana Múltiple , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Compuestos de Alumbre/administración & dosificación , Femenino , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Modelos Animales de Enfermedad

RESUMEN

Schoepfia schreberi has been used in Mayan folk medicine to treat diarrhea and cough. This study aimed to determine the anti-growth, anti-resistance, and/or anti-virulence activities of S. schreberi extracts against Acinetobacter baumannii, a pathogen leader that causes healthcare-associated infections with high rates of drug-resistant including carbapenems, the last line of antibiotics known as superbugs, and analyze their composition using HPLC-DAD. Ethyl acetate (SSB-3) and methanol (SSB-4) bark extracts exhibit antimicrobial and biocidal effects against drug-susceptible and drug-resistant A. baumannii. Chemical analysis revealed that SSB-3 and SSB-4 contained of gallic and ellagic acids derivatives. The anti-resistance activity of the extracts revealed that SSB-3 or SSB-4, combined with imipenem, exhibited potent antibiotic reversal activity against A. baumannii by acting as pump efflux modulators. The extracts also displayed activity against surface motility of A. baumannii and its capacity to survive reactive oxygen species. This study suggests that S. schreberi can be considered a source of antibiotics, even adjuvanted compounds, as anti-resistant or anti-virulence agents against A. baumannii, contributing to ethnopharmacological knowledge and reappraisal of Mayan medicinal flora, and supporting the traditional use of the bark of the medicinal plant S. schreberi for the treatment of infectious diseases.

RESUMEN

Introduction: The Acinetobacter calcoaceticus-Acinetobacter baumannii complex, or Acb complex, consists of six species: Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter nosocomialis, Acinetobacter pittii, Acinetobacter seifertii, and Acinetobacter lactucae. A. baumannii is the most clinically significant of these species and is frequently related to healthcare-associated infections (HCAIs). Clustered regularly interspaced short palindromic repeat (CRISPR) arrays and associated genes (cas) constitute bacterial adaptive immune systems and function as variable genetic elements. This study aimed to conduct a genomic analysis of Acb complex genomes available in databases to describe and characterize CRISPR systems and cas genes. Methods: Acb complex genomes available in the NCBI and BV-BRC databases, the identification and characterization of CRISPR-Cas systems were performed using CRISPRCasFinder, CRISPRminer, and CRISPRDetect. Sequence types (STs) were determined using the Oxford scheme and ribosomal multilocus sequence typing (rMLST). Prophages were identified using PHASTER and Prophage Hunter. Results: A total of 293 genomes representing six Acb species exhibited CRISPR-related sequences. These genomes originate from various sources, including clinical specimens, animals, medical devices, and environmental samples. Sequence typing identified 145 ribosomal multilocus sequence types (rSTs). CRISPR-Cas systems were confirmed in 26.3% of the genomes, classified as subtypes I-Fa, I-Fb and I-Fv. Probable CRISPR arrays and cas genes associated with CRISPR-Cas subtypes III-A, I-B, and III-B were also detected. Some of the CRISPR-Cas systems are associated with genomic regions related to Cap4 proteins, and toxin-antitoxin systems. Moreover, prophage sequences were prevalent in 68.9% of the genomes. Analysis revealed a connection between these prophages and CRISPR-Cas systems, indicating an ongoing arms race between the bacteria and their bacteriophages. Furthermore, proteins associated with anti-CRISPR systems, such as AcrF11 and AcrF7, were identified in the A. baumannii and A. pittii genomes. Discussion: This study elucidates CRISPR-Cas systems and defense mechanisms within the Acb complex, highlighting their diverse distribution and interactions with prophages and other genetic elements. This study also provides valuable insights into the evolution and adaptation of these microorganisms in various environments and clinical settings.

RESUMEN

In recent years, humanity has begun to face a growing challenge posed by a rise in the prevalence of antibiotic-resistant bacteria. This has resulted in an alarming surge in fatalities and the emergence of increasingly hard-to-manage diseases. Acinetobacter baumannii can be seen as one of these resilient pathogens due to its increasing prevalence in hospitals, its resistance to treatment, and its association with elevated mortality rates. Despite its clinical significance, the scientific understanding of this pathogen in non-hospital settings remains limited. Knowledge of its virulence factors is also lacking. Therefore, in this review, we seek to shed light on the latest research regarding the ecological niches, microbiological traits, and antibiotic resistance profiles of Acinetobacter baumannii. Recent studies have revealed the presence of this bacterium in a growing range of environmental niches, including rivers, treatment plants, and soils. It has also been discovered in diverse food sources such as meat and vegetables, as well as in farm animals and household pets such as dogs and cats. This broader presence of Acinetobacter baumannii, i.e., outside of hospital environments, indicates a significant risk of environmental contamination. As a result, greater levels of awareness and new preventive measures should be promoted to address this potential threat to public health.

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Introduction: Antibiotic-resistant Acinetobacter baumannii is a very important nosocomial pathogen worldwide. Thousands of studies have been conducted about this pathogen. However, there has not been any attempt to use all this information to highlight the research trends concerning this pathogen. Methods: Here we use unsupervised learning and natural language processing (NLP), two areas of Artificial Intelligence, to analyse the most extensive database of articles created (5,500+ articles, from 851 different journals, published over 3 decades). Results: K-means clustering found 113 theme clusters and these were defined with representative terms automatically obtained with topic modelling, summarising different research areas. The biggest clusters, all with over 100 articles, are biased toward multidrug resistance, carbapenem resistance, clinical treatment, and nosocomial infections. However, we also found that some research areas, such as ecology and non-human infections, have received very little attention. This approach allowed us to study research themes over time unveiling those of recent interest, such as the use of Cefiderocol (a recently approved antibiotic) against A. baumannii. Discussion: In a broader context, our results show that unsupervised learning, NLP and topic modelling can be used to describe and analyse the research themes for important infectious diseases. This strategy should be very useful to analyse other ESKAPE pathogens or any other pathogens relevant to Public Health.

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Antibiotic overuse and the resulting antimicrobial resistance pose significant global public health challenges, providing an avenue for opportunistic pathogens like Acinetobacter baumannii to thrive. This study will report the trends of Acinetobacter baumannii antimicrobial resistance patterns at the Hospital Teodoro Maldonado Carbo, Ecuador. An observational, analytical, longitudinal, and prospective study was conducted involving patients diagnosed with hospital-acquired infections. Antimicrobial susceptibility testing was performed, followed by molecular analysis of carbapenemase genes in Acinetobacter baumannii isolates. We included 180 patients aged from 16 to 93 years. The hospital mortality rate was 63/180 (35%). Invasive mechanical ventilation (IMV) was indicated in 91/180 patients (50.4%). The overall survival (OS) rate in patients on IMV was 49.5% (45/91), with a median survival of 65 days. The OS rate in patients not on IMV was 80.9% (72/89), with a median survival of 106 days (HR 2.094; 95% CI 1.174-3.737; p = 0.012). From multivariate analysis, we conclude that ventilator-associated pneumonia is the most related factor to OS.

RESUMEN

Acinetobacter baumannii has been described as a cause of serious community-acquired infections in tropical countries. Currently, its implications when simultaneously identified with other pathogens are not yet adequately understood. A descriptive study was conducted on hospitalized patients with a diagnosis of moderate/severe SARS-CoV-2-induced pneumonia confirmed via real-time RT-PCR. Patients aged > 18 years who were admitted to a specialized COVID-19 treatment center in Peru were selected for enrollment. A. baumannii was detected via the PCR amplification of the blaOXA-51 gene obtained from nasopharyngeal swabs within 48 h of hospitalization. A total of 295 patients with COVID-19 who met the study inclusion criteria were enrolled. A. baumannii was simultaneously identified in 40/295 (13.5%) of COVID-19-hospitalized patients. Demographic data and comorbidities were comparable in both Acinetobacter-positive and -negative subgroups. However, patients identified as being infected with Acinetobacter were more likely to have received outpatient antibiotics prior to hospitalization, had a higher requirement for high-flow nasal cannula and a higher subjective incidence of fatigue, and were more likely to develop Acinetobacter-induced pneumonia during hospitalization. Conclusions: The group in which SARS-CoV-2 and A. baumannii were simultaneously identified had a higher proportion of fatigue, a higher frequency of requiring a high-flow cannula, and a higher proportion of superinfection with the same microorganism during hospitalization.

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Acinetobacter pneumonia is a significant healthcare-associated infection that poses a considerable challenge to clinicians due to its multidrug-resistant nature. Recent world events, such as the COVID-19 pandemic, have highlighted the need for effective treatment and management strategies for Acinetobacter pneumonia. In this review, we discuss lessons learned from recent world events, particularly the COVID-19 pandemic, in the context of the treatment and management of Acinetobacter pneumonia. We performed an extensive literature review to uncover studies and information pertinent to the topic. The COVID-19 pandemic underscored the importance of infection control measures in healthcare settings, including proper hand hygiene, isolation protocols, and personal protective equipment use, to prevent the spread of multidrug-resistant pathogens like Acinetobacter. Additionally, the pandemic highlighted the crucial role of antimicrobial stewardship programs in optimizing antibiotic use and curbing the emergence of resistance. Advances in diagnostic techniques, such as rapid molecular testing, have also proven valuable in identifying Acinetobacter infections promptly. Furthermore, due to the limited availability of antibiotics for treating infections caused A. baumannii, alternative strategies are needed like the use of antimicrobial peptides, bacteriophages and their enzymes, nanoparticles, photodynamic and chelate therapy. Recent world events, particularly the COVID-19 pandemic, have provided valuable insights into the treatment and management of Acinetobacter pneumonia. These lessons emphasize the significance of infection control, antimicrobial stewardship, and early diagnostics in combating this challenging infection.

RESUMEN

The surge in multidrug-resistant pathogens worldwide has jeopardized the clinical efficiency of many current antibiotics. This problem steered many researchers in their quest to discover new effective antimicrobial agents from natural origins including plants or their residing endophytes. In this work, we aimed to identify the endophytic fungi derived from Hedera helix L. and investigate their potential antimicrobial activity. Bioguided fractionation approach was conducted to isolate the pure compounds from the most active fungal fraction. Out of a total of six different isolated endophytic fungal strains, only Aspergillus cejpii showed the highest activity against all tested microbial strains. The most active fraction was the dichloromethane/methanol fraction (DCM:MeOH), where it showed significant activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Serratia marcescens, Acinetobacter baumannii, Salmonella typhi, and three drug-resistant clinical isolate strains including Methicillin-resistant Staphylococcus aureus (MRSA, H1), Pseudomonas aeruginosa (PS 16), and Acinetobacter baumannii (ACT 322) using tetracyline and kanamycin as the control antibiotics. Bioguided fractionation of the active fraction led to the isolation of the γ-butenolide, spiculisporic acid. Structure elucidation was carried out using 1H and 13C-NMR spectroscopic analysis. The compound showed good antimicrobial activities with minimum inhibitory concentration (MIC) values ranging from 3.9 to 31.25 µg/mL against all tested strains. Gas chromatography coupled to mass spectrometry (GC-MS) profiling was also carried out to identify the metabolites in the microbial crude extract. In conclusion, endophytic fungi, Aspergillus cejpii, isolated from Hedera helix L. roots showed promising antimicrobial activity which merits further in-depth investigations for potential utilization as a source of new antibiotics in the future. It can also be considered as a novel source for spiculisporic acid.

Asunto(s)

Antiinfecciosos , Aspergillus , Hedera , Staphylococcus aureus Resistente a Meticilina , Antibacterianos/química , Antiinfecciosos/farmacología , Pruebas de Sensibilidad Microbiana , Hongos