Lactate metabolism promotes in vivo fitness during Acinetobacter baumannii infection.

Autor:	Morris FC; Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia.; Centre to Impact AMR, Monash University, Clayton, Victoria 3800, Australia., Jiang Y; Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia.; Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310016, China., Fu Y; Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia.; Department of Clinical Laboratory, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310016, China., Kostoulias X; Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia.; Centre to Impact AMR, Monash University, Clayton, Victoria 3800, Australia.; Department of Infectious Diseases, The Alfred Hospital and School of Translational Medicine, Monash University, Melbourne, Victoria 3004, Australia., Murray GL; Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia.; Present Address; Royal Women's Hospital, Grattan Street, Parkville, Victoria 3052, Australia., Yu Y; Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310016, China., Peleg AY; Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia.; Centre to Impact AMR, Monash University, Clayton, Victoria 3800, Australia.; Department of Infectious Diseases, The Alfred Hospital and School of Translational Medicine, Monash University, Melbourne, Victoria 3004, Australia.
Jazyk:	angličtina
Zdroj:	FEMS microbiology letters [FEMS Microbiol Lett] 2024 Jan 09; Vol. 371.
DOI:	10.1093/femsle/fnae032
Abstrakt:	Acinetobacter baumannii is one of the most prevalent causes of nosocomial infections worldwide. However, a paucity of information exists regarding the connection between metabolic capacity and in vivo bacterial fitness. Elevated lactate is a key marker of severe sepsis. We have previously shown that the putative A. baumannii lactate permease gene, lldP, is upregulated during in vivo infection. Here, we confirm that lldP expression is upregulated in three A. baumannii strains during a mammalian systemic infection. Utilising a transposon mutant disrupted for lldP in the contemporary clinical strain AB5075-UW, and a complemented strain, we confirmed its role in the in vitro utilisation of l-(+)-lactate. Furthermore, disruption of the lactate metabolism pathway resulted in reduced bacterial fitness during an in vivo systemic murine competition assay. The disruption of lldP had no impact on the susceptibility of this strain to complement mediated killing by healthy human serum. However, growth in biologically relevant concentrations of lactate observed during severe sepsis, led to bacterial tolerance to killing by healthy human blood, a phenotype that was abolished in the lldP mutant. This study highlights the importance of the lactate metabolism pathway for survival and growth of A. baumannii during infection. (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)
Databáze:	MEDLINE
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