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Colistin-degrading proteases confer collective resistance to microbial communities during polymicrobial infections.
Lee, Do-Hoon; Cha, Ju-Hee; Kim, Dae-Wi; Lee, Kihyun; Kim, Yong-Seok; Oh, Hyo-Young; Cho, You-Hee; Cha, Chang-Jun.
Afiliación
  • Lee DH; Department of Systems Biotechnology and Center for Antibiotic Resistome, Chung-Ang University, Anseong, 17456, Republic of Korea.
  • Cha JH; Department of Systems Biotechnology and Center for Antibiotic Resistome, Chung-Ang University, Anseong, 17456, Republic of Korea.
  • Kim DW; Department of Systems Biotechnology and Center for Antibiotic Resistome, Chung-Ang University, Anseong, 17456, Republic of Korea.
  • Lee K; Division of Life Sciences, Jeonbuk National University, Jeonju, 54896, Republic of Korea.
  • Kim YS; Department of Systems Biotechnology and Center for Antibiotic Resistome, Chung-Ang University, Anseong, 17456, Republic of Korea.
  • Oh HY; Department of Systems Biotechnology and Center for Antibiotic Resistome, Chung-Ang University, Anseong, 17456, Republic of Korea.
  • Cho YH; Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam, 13488, Republic of Korea.
  • Cha CJ; Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam, 13488, Republic of Korea.
Microbiome ; 10(1): 129, 2022 08 19.
Article en En | MEDLINE | ID: mdl-35982474
BACKGROUND: The increasing prevalence of resistance against the last-resort antibiotic colistin is a significant threat to global public health. Here, we discovered a novel colistin resistance mechanism via enzymatic inactivation of the drug and proposed its clinical importance in microbial communities during polymicrobial infections. RESULTS: A bacterial strain of the Gram-negative opportunistic pathogen Stenotrophomonas maltophilia capable of degrading colistin and exhibiting a high-level colistin resistance was isolated from the soil environment. A colistin-degrading protease (Cdp) was identified in this strain, and its contribution to colistin resistance was demonstrated by growth inhibition experiments using knock-out (Δcdp) and complemented (Δcdp::cdp) mutants. Coculture and coinfection experiments revealed that S. maltophilia carrying the cdp gene could inactivate colistin and protect otherwise susceptible Pseudomonas aeruginosa, which may seriously affect the clinical efficacy of the drug for the treatment of cystic fibrosis patients with polymicrobial infection. CONCLUSIONS: Our results suggest that Cdp should be recognized as a colistin resistance determinant that confers collective resistance at the microbial community level. Our study will provide vital information for successful clinical outcomes during the treatment of complex polymicrobial infections, particularly including S. maltophilia and other colistin-susceptible Gram-negative pathogens such as P. aeruginosa. Video abstract.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Bacterias Gramnegativas / Farmacorresistencia Bacteriana Múltiple / Coinfección / Microbiota Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Microbiome Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Bacterias Gramnegativas / Farmacorresistencia Bacteriana Múltiple / Coinfección / Microbiota Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Microbiome Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido