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Small non-coding RNAs (sRNAs) are a key part of gene expression regulation in bacteria. Many physiologic activities like adaptation to environmental stresses, antibiotic resistance, quorum sensing, and modulation of the host immune response are regulated directly or indirectly by sRNAs in Gram-negative bacteria. Therefore, sRNAs can be considered as potentially useful therapeutic options. They have opened promising perspectives in the field of diagnosis of pathogens and treatment of infections caused by antibiotic-resistant organisms. Identification of sRNAs can be executed by sequence and expression-based methods. Despite the valuable progress in the last two decades, and discovery of new sRNAs, their exact role in biological pathways especially in co-operation with other biomolecules involved in gene expression regulation such as RNA-binding proteins (RBPs), riboswitches, and other sRNAs needs further investigation. Although the numerous RNA databases are available, including 59 databases used by RNAcentral, there remains a significant gap in the absence of a comprehensive and professional database that categorizes experimentally validated sRNAs in Gram-negative pathogens. Here, we review the present knowledge about most recent and important sRNAs and their regulatory mechanism, strengths and weaknesses of current methods of sRNAs identification. Also, we try to demonstrate the potential applications and new insights of sRNAs for future studies.

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The threat of methicillin-resistant Staphylococcus aureus (MRSA) is increasing worldwide, making it significantly necessary to discover a novel way of dealing with related infections. The quick spread of MRSA isolates among infected individuals has heightened public health concerns and significantly limited treatment options. Vancomycin (VAN) can be applied to treat severe MRSA infections, and the indiscriminate administration of this antimicrobial agent has caused several concerns in medical settings. Owing to several advantageous characteristics, a niosomal drug delivery system may increase the potential of loaded antimicrobial agents. This work aims to examine the antibacterial and anti-biofilm properties of VAN-niosome against MRSA clinical isolates with emphasis on cytotoxicity and stability studies. Furthermore, we aim to suggest an effective approach against MRSA infections by investigating the inhibitory effect of formulated niosome on the expression of the biofilm-associated gene (icaR). The thin-film hydration approach was used to prepare the niosome (Tween 60, Span 60, and cholesterol), and field emission scanning electron microscopy (FE-SEM), an in vitro drug release, dynamic light scattering (DLS), and entrapment efficiency (EE%) were used to investigate the physicochemical properties. The physical stability of VAN-niosome, including hydrodynamic size, polydispersity index (PDI), and EE%, was analyzed for a 30-day storage time at 4 °C and 25 °C. In addition, the human foreskin fibroblast (HFF) cell line was used to evaluate the cytotoxic effect of synthesized niosome. Moreover, minimum inhibitory and bactericidal concentrations (MICs/MBCs) were applied to assess the antibacterial properties of niosomal VAN formulation. Also, the antibiofilm potential of VAN-niosome was investigated by microtiter plate (MTP) and real-time PCR methods. The FE-SEM result revealed that synthesized VAN-niosome had a spherical morphology. The hydrodynamic size and PDI of VAN-niosome reported by the DLS method were 201.2 nm and 0.301, respectively. Also, the surface zeta charge of the prepared niosome was - 35.4 mV, and the EE% ranged between 58.9 and 62.5%. Moreover, in vitro release study revealed a sustained-release profile for synthesized niosomal formulation. Our study showed that VAN-niosome had acceptable stability during a 30-day storage time. Additionally, the VAN-niosome had stronger antibacterial and anti-biofilm properties against MRSA clinical isolates compared with free VAN. In conclusion, the result of our study demonstrated that niosomal VAN could be promising as a successful drug delivery system due to sustained drug release, negligible toxicity, and high encapsulation capacity. Also, the antibacterial and anti-biofilm studies showed the high capacity of VAN-niosome against MRSA clinical isolates. Furthermore, the results of real-time PCR exhibited that VAN-niosome could be proposed as a powerful strategy against MRSA biofilm via down-regulation of icaR gene expression.

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Interactions between the gut microbiota and host immunity are sophisticated, dynamic, and host-dependent. Scientists have recently conducted research showing that disturbances in the gut bacterial community can lead to a decrease in some metabolites and, consequently, to behaviors such as depression. Exposure to stressors dropped the relative abundance of bacteria in the genus Bacteroides while soaring the relative abundance of bacteria in the genus Clostridium, Coprococcus, Dialister, and Oscillibacter, which were also reduced in people with depression. Microbiota and innate immunity are in a bilateral relationship. The gut microbiota has been shown to induce the synthesis of antimicrobial proteins such as catalysidins, type C lectins, and defensins. Probiotic bacteria can modulate depressive behavior through GABA signaling. The gut microbiome produces essential metabolites such as neurotransmitters, tryptophan metabolites, and short-chain fatty acids (SCFAs) that can act on the CNS. In the case of dysbiosis, due to mucin changes, the ratio of intestinal-derived molecules may change and contribute to depression. Psychotropics, including Bifidobacterium longum NCC3001, Clostridium butyricum CBM588, and Lactobacillus acidophilus, have mental health benefits, and can have a positive effect on the host-brain relationship, and have antidepressant effects. This article reviews current studies on the association between gut microbiota dysbiosis and depression. Comprehensively, these findings could potentially lead to novel approaches to improving depressive symptoms via gut microbiota alterations, including probiotics, prebiotics, and fecal microbiota transplantation.

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The Increase in infections caused by resistant strains of Pseudomonas aeruginosa poses a formidable challenge to global healthcare systems. P. aeruginosa is capable of causing severe human infections across diverse anatomical sites, presenting considerable therapeutic obstacles due to its heightened drug resistance. Niosomal drug delivery systems offer enhanced pharmaceutical potential for loaded contents due to their desirable properties, mainly providing a controlled-release profile. This study aimed to formulate an optimized niosomal drug delivery system incorporating stearylamine (SA) to augment the anti-bacterial and anti-biofilm activities of quercetin (QCT) against both standard and clinical strains of P. aeruginosa. QCT-loaded niosome (QCT-niosome) and QCT-loaded SA- niosome (QCT-SA- niosome) were synthesized by the thin-film hydration technique, and their physicochemical characteristics were evaluated by field emission scanning electron microscopy (FE-SEM), zeta potential measurement, entrapment efficacy (EE%), and in vitro release profile. The anti-P. aeruginosa activity of synthesized niosomes was assessed using minimum inhibitory and bactericidal concentrations (MICs/MBCs) and compared with free QCT. Additionally, the minimum biofilm inhibitory and eradication concentrations (MBICs/MBECs) were carried out to analyze the ability of QCT-niosome and QCT-SA-niosome against P. aeruginosa biofilms. Furthermore, the cytotoxicity assay was conducted on the L929 mouse fibroblasts cell line to evaluate the biocompatibility of the formulated niosomes. FE-SEM analysis revealed that both synthesized niosomal formulations exhibited spherical morphology with different sizes (57.4 nm for QCT-niosome and 178.9 nm for QCT-SA-niosome). The EE% for cationic and standard niosomal formulations was reported at 75.9% and 59.6%, respectively. Both formulations showed an in vitro sustained-release profile, and QCT-SA-niosome exhibited greater stability during a 4-month storage time compared to QCT-niosome. Microbial experiments indicated that both prepared formulations had higher anti-bacterial and anti-biofilm activities than free QCT. Also, the QCT-SA-niosome exhibited greater reductions in MIC, MBC, MBIC, and MBEC values compared to the QCT-niosome at equivalent concentrations. This study supports the potential of QCT-niosome and QCT-SA-niosome as effective agents against P. aeruginosa infections, manifesting significant anti-bacterial and anti-biofilm efficacy alongside biocompatibility with L929 cell lines. Furthermore, our results suggest that optimized QCT-niosome with cationic lipids could efficiently target P. aeruginosa cells with negligible cytotoxic effect.

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Background: The interaction between commensal bacteria and the host is essential for health and the gut microbiota-brain axis plays a vital role in this regard. Obesity as a medical problem not only affect the health of the individuals, but also the economic and social aspects of communities. The presence of any dysbiosis in the composition of the gut microbiota disrupts in the gut microbiota-brain axis, which in turn leads to an increase in appetite and then obesity. Because common treatments for obesity have several drawbacks, the use of microbiota-based therapy in addition to treatment and prevention of obesity can have other numerous benefits for the individual. In this review, we intend to investigate the relationship between obesity and the gut microbiota-brain axis as well as novel treatment strategies based on this axis with an emphasis on gut microbiota.

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A nanoparticle-drug delivery system against Staphylococcus aureus, especially Methicillin-resistant staphylococcus aureus, has been recently proposed as an alternative pathway therapy. Methicillin-resistant staphylococcus aureus is resistance to many antibiotics, making it a a threat to human life, especially for older and immunocompromised people. Treatment of Multidrug-resistant staphylococcus aureus is considered an urgent need. A variety of kinds of nanoparticle-drug delivery systems with different compositions, and biological properties have been extensively investigated against Staphylococcus aureus. This review summarizes the novel nanoparticle-drug delivery systems against Staphylococcus aureus. These nanoparticle-drug delivery systems could reduce antibiotic resistance and minimize side effects of the antibiotics. Also, they can deliver a high concentration of the drugs and eliminate the bacteria in a specific and targeted site of infection. Despite these benefits of nanoparticle-drug delivery systems, the cytotoxicity, stress oxidative, genotoxicity, and inflammation that may occur in vivo and in vitro should not be ignored. Therefore, we need a better knowledge of the pharmacological properties and safety concerns of nanoparticle-drug delivery systems. The limitations of each nanoparticle-drug delivery system with high therapeutic potential have to be considered for further design.

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BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen in the health-care systems and one of the primary causative agents with high mortality in hospitalized patients, particularly immunocompromised. The limitation of effective antibiotic administration in multidrug-resistant and extensively drug-resistant P. aeruginosa isolates leads to the development of nosocomial infections and health problems. Quorum sensing system contributes to biofilm formation, expression of bacterial virulence factors, and development of drug resistance, causing prolonged patient infections. Therefore, due to the significance of the quorum sensing system in increasing the pathogenicity of P. aeruginosa, the primary objective of our study was to investigate the frequency of quorum sensing genes, as well as the biofilm formation and antibiotic resistance pattern among P. aeruginosa strains. METHODS: A total of 120 P. aeruginosa isolates were collected from different clinical specimens. The disk diffusion method was applied to detect the antibiotic resistance pattern of P. aeruginosa strains. Also, the microtiter plate method was carried out to evaluate the biofilm-forming ability of isolates. Finally, the frequency of rhlI, rhlR, lasI, and lasR genes was examined by the polymerase chain reaction method. RESULTS: In total, 88.3% P. aeruginosa isolates were found to be multidrug-resistant, of which 30.1% had extensively drug-resistant pattern. The highest and lowest resistance rates were found against ceftazidime (75.0%) and ciprofloxacin (46.6%), respectively. Also, 95.8% of isolates were able to produce biofilm, of which 42.5%, 33.3%, and 20.0% had strong, moderate, and weak biofilm patterns, respectively. The frequency of quorum sensing genes among all examined strains was as follows: rhlI (81.6%), rhlR (90.8%), lasI (89.1%), and lasR (78.3%). The most common type of quorum sensing genes among multidrug-resistant isolates were related to rhlR and lasI genes with 94.3%. Furthermore, rhlI, rhlR, and lasI genes were positive for all extensively drug-resistant isolates. However, the lasR gene had the lowest frequency among both multidrug-resistant (83.0%) and extensively drug-resistant (90.6%) isolates. Moreover, rhlR (94.7%) and lasR (81.7%) genes had the highest and lowest prevalence among biofilm-forming isolates, respectively. CONCLUSION: Our findings disclosed the significantly high prevalence of drug resistance among P. aeruginosa isolates. Also, the quorum sensing system had a significant correlation with biofilm formation and drug resistance, indicating the essential role of this system in the emergence of nosocomial infections caused by P. aeruginosa.

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Due to high antimicrobial resistance and biofilm-forming ability, Pseudomonas aeruginosa is one of the seriously life-threatening agents causing chronic and nosocomial infections. This study was performed to determine the antibiotic resistance pattern, biofilm formation, and frequency of biofilm-related genes in P. aeruginosa strains. In total, 123 P. aeruginosa isolates were collected from different clinical sources. Antimicrobial susceptibility testing (AST) was performed to detect multidrug-resistant P. aeruginosa (MDRPA) isolates. To evaluate the biofilm-forming isolates, the microtiter plate (MTP) method was carried out. Also, the prevalence of biofilm genotype patterns, including pslA, pslD, pelA, pelF, and algD genes, was detected by polymerases chain reaction (PCR). According to our findings, the highest resistance and susceptibility rates were found in ceftazidime with 74.7% (n = 92) and ciprofloxacin with 42.2% (n = 52), respectively. In our study, the highest level of antibiotic resistance belonged to wound isolates which meropenem had the most antibacterial activity against them. In total, 86.1% (n = 106) P. aeruginosa isolates were determined as MDRPA, of which 61.3% (n = 65) were able to form strong biofilm. The highest and lowest frequency of biofilm-related genes among biofilm producer isolates belonged to pelF with 82.1% (n = 101) and algD with 55.2% (n = 68), respectively. The findings of the conducted study indicate a significant relationship between MDRPA and biofilm genotypic/phenotypic patterns, suggesting the necessity of a careful surveillance program in hospital settings.

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Chronic rhinosinusitis (CRS) is a pathological condition characterized by persistent inflammation in the upper respiratory tract and paranasal sinuses. The epithelium serves as the first line of defense against potential threats and protects the nasal mucosa. The fundamental mechanical barrier is formed by the cell-cell contact and mucociliary clearance (MCC) systems. The physical-mechanical barrier is comprised of many cellular structures, including adhesion junctions and tight junctions (TJs). To this end, different factors, such as the dysfunction of MCC, destruction of epithelial barriers, and tissue remodeling, are related to the onset and development of CRS. Recently published studies reported the critical role of different microorganisms, such as Staphylococcus aureus and Pseudomonas aeruginosa, in the induction of the mentioned factors. Bacteria could result in diminished ciliary stimulation capacity, and enhance the chance of CRS by reducing basal ciliary beat frequency. Additionally, bacterial exoproteins have been demonstrated to disrupt the epithelial barrier and induce downregulation of transmembrane proteins such as occludin, claudin, and tricellulin. Moreover, bacteria exert an influence on TJ proteins, leading to an increase in the permeability of polarized epithelial cells. Noteworthy, it is evident that the activation of TLR2 by staphylococcal enterotoxin can potentially undermine the structural integrity of TJs and the epithelial barrier through the induction of pro-inflammatory cytokines. The purpose of this article is an attempt to investigate the possible role of the most important microorganisms associated with CRS and their pathogenic mechanisms against mucosal surfaces and epithelial barriers in the paranasal sinuses. Video Abstract.

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Multidrug-resistant pathogens are one of the common causes of death in burn patients and have a high risk of nosocomial infections, especially pneumonia, urinary tract infections, and cellulitis. The role of prolonged hospitalization and empirical antibiotics administration in developing multidrug-resistant pathogens is undeniable. In the early days of admitting burn patients, Gram-positive bacteria were the dominant isolates with a more sensitive antibiotic pattern. However, the emergence of Gram-negative bacteria that are more resistant later occurs. Trustworthy guideline administration in burn wards is one of the strategies to prevent multidrug-resistant pathogens. Also, a multidisciplinary therapeutic approach is an effective way to avoid antibiotic resistance that involves infectious disease specialists, pharmacists, and burn surgeons. However, the emerging resistance to conventional antimicrobial approaches (such as systemic antibiotic exposure, traditional wound dressing, and topical antibiotic ointments) among burn patients has challenged the treatment of multidrug-resistant infections, and using nanoparticles is a suitable alternative. In this review article, we will discuss different aspects of multidrug-resistant pathogens in burn wounds, emphasizing the full role of these pathogens in burn wounds and discussing the application of nanotechnology in dealing with them. Also, some advances in various types of nanomaterials, including metallic nanoparticles, liposomes, hydrogels, carbon quantum dots, and solid lipid nanoparticles in burn wound healing, will be explained.

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Escherichia coli sequence type 131 (ST131) is a multidrug-resistant strain with the global dissemination. Biofilm formation-related factors include the most important virulence factors in extra-intestinal pathogenic E. coli (ExPEC) ST131 strains causing infections with treatment-limited subjects. This study aims to investigate the biofilm formation ability and its correlation with the presence of fimH, afa, and kpsMSTII genes in clinical isolates of ExPEC ST131. In this regard, the prevalence and characteristics of these strains collected and evaluated. The results revealed strong, moderate, and weak attachment abilities related to biofilm formation attributes in 45%, 20%, and 35% of strains, respectively. In the meantime, the frequency of the fimH, afa, and kpsMSTII genes among the isolates was observed as follows: fimH positive: 65%; afa positive: 55%; and kpsMSTII positive: 85%. The results convey a significant different of biofilm formation ability between clinical E. coli ST131 and non-ST131 isolates. Furthermore, while 45% of ST131 isolates produced strong biofilms, only 2% of non-ST131 isolates showed the ability to form strong biofilms. The attending of fimH, afa, and kpsMSTII genes in the majority of ST131 strains demonstrated a key role leading to biofilm formation. These findings suggested the application of fimH, afa, and kpsMSTII gene suppressors for treating biofilm infections caused by drug-resistant ST131 strains.

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Infective endocarditis (IE) is a severe disease that is still associated with high mortality despite recent advances in diagnosis and treatment. HACEK organisms (Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae) are gram-negative bacteria that are part of the normal flora of the mouth and upper respiratory tract in humans. These organisms cause a wide range of infections, of which IE is one of the most notable. In order to control and prevent endocarditis caused by HACEK, measures such as oral hygiene and the use of prophylactic drugs should be used for people at risk, including people with underlying heart disease and people with artificial valves. This review is a summary of the main aspects of IE focusing on HACEK organisms.

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