mleS in Staphylococcus aureus Contributes to Microaerobic Metabolic Activity, Abscess Formation, and Survival in Macrophages

ABSTRACT Staphylococcus aureus is subdivided into lineages termed sequence types (STs), infections of which necessitate the expression of virulence factors and metabolic adaptation to the host niche. Given that mechanisms underlying the dynamic replacement of sequence types in S. aureus populations...

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Main Authors: Fengning Chen, Yuyao Yin, Hongbin Chen, Shuguang Li, Guankun Yin, Hui Wang
Format: Article
Language:English
Published: American Society for Microbiology 2023-06-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.00909-23
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author Fengning Chen
Yuyao Yin
Hongbin Chen
Shuguang Li
Guankun Yin
Hui Wang
author_facet Fengning Chen
Yuyao Yin
Hongbin Chen
Shuguang Li
Guankun Yin
Hui Wang
author_sort Fengning Chen
collection DOAJ
description ABSTRACT Staphylococcus aureus is subdivided into lineages termed sequence types (STs), infections of which necessitate the expression of virulence factors and metabolic adaptation to the host niche. Given that mechanisms underlying the dynamic replacement of sequence types in S. aureus populations have yet to be sufficiently determined, we investigated the role of metabolic determinants in epidemic clones. mleS, encoding the NAD+-dependent malolactic enzyme, was found to be carried by the epidemic clones ST59 and ST398, although not by ST239 and ST5. The genomic location of mleS in the metabolism-associated region flanked by the thiol-specific redox system and glycolysis operon implies that it plays significant roles in metabolism and pathogenesis. Mouse skin abscess caused by the BS19-mleS mutant strain (isogenic mleS mutant in an ST59 isolate) was significantly attenuated and associated with reductions in interleukin-6 (IL-6) and lactic acid production. mleS deletion also impaired S. aureus biofilm formation and survival in RAW264.7 cells. The BS19-mleS-mutant was also characterized by reduced ATP and lactic acid production under microaerobic conditions; however, NAD+/NADH levels remained unaffected. mleS is thus identified as an epidemiological marker that plays an important role in the microaerobic metabolism and pathogenesis of epidemic S. aureus clones. IMPORTANCE Given the importance of metabolic adaptation during infection, new insights are required regarding the pathogenesis of S. aureus, particularly for epidemic clones. We accordingly investigated the role of metabolic determinants that are unique to the epidemic clones ST59 and ST398. Our results provide evidence that the NAD+-dependent malolactic enzyme-coding gene mleS is an epidemiological marker that plays an important role in the microaerobic metabolism and pathogenesis of epidemic S. aureus clones.
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spelling doaj.art-178aa7936a584d4d8d3232545a98896d2023-06-15T13:18:32ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-06-0111310.1128/spectrum.00909-23mleS in Staphylococcus aureus Contributes to Microaerobic Metabolic Activity, Abscess Formation, and Survival in MacrophagesFengning Chen0Yuyao Yin1Hongbin Chen2Shuguang Li3Guankun Yin4Hui Wang5Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, ChinaDepartment of Clinical Laboratory, Peking University People’s Hospital, Beijing, ChinaDepartment of Clinical Laboratory, Peking University People’s Hospital, Beijing, ChinaDepartment of Clinical Laboratory, Peking University People’s Hospital, Beijing, ChinaDepartment of Clinical Laboratory, Peking University People’s Hospital, Beijing, ChinaDepartment of Clinical Laboratory, Peking University People’s Hospital, Beijing, ChinaABSTRACT Staphylococcus aureus is subdivided into lineages termed sequence types (STs), infections of which necessitate the expression of virulence factors and metabolic adaptation to the host niche. Given that mechanisms underlying the dynamic replacement of sequence types in S. aureus populations have yet to be sufficiently determined, we investigated the role of metabolic determinants in epidemic clones. mleS, encoding the NAD+-dependent malolactic enzyme, was found to be carried by the epidemic clones ST59 and ST398, although not by ST239 and ST5. The genomic location of mleS in the metabolism-associated region flanked by the thiol-specific redox system and glycolysis operon implies that it plays significant roles in metabolism and pathogenesis. Mouse skin abscess caused by the BS19-mleS mutant strain (isogenic mleS mutant in an ST59 isolate) was significantly attenuated and associated with reductions in interleukin-6 (IL-6) and lactic acid production. mleS deletion also impaired S. aureus biofilm formation and survival in RAW264.7 cells. The BS19-mleS-mutant was also characterized by reduced ATP and lactic acid production under microaerobic conditions; however, NAD+/NADH levels remained unaffected. mleS is thus identified as an epidemiological marker that plays an important role in the microaerobic metabolism and pathogenesis of epidemic S. aureus clones. IMPORTANCE Given the importance of metabolic adaptation during infection, new insights are required regarding the pathogenesis of S. aureus, particularly for epidemic clones. We accordingly investigated the role of metabolic determinants that are unique to the epidemic clones ST59 and ST398. Our results provide evidence that the NAD+-dependent malolactic enzyme-coding gene mleS is an epidemiological marker that plays an important role in the microaerobic metabolism and pathogenesis of epidemic S. aureus clones.https://journals.asm.org/doi/10.1128/spectrum.00909-23NAD+-dependent malolactic enzyme coding gene (mleS)Staphylococcus aureusmacrophage survivalmetabolismmouse skin abscess
spellingShingle Fengning Chen
Yuyao Yin
Hongbin Chen
Shuguang Li
Guankun Yin
Hui Wang
mleS in Staphylococcus aureus Contributes to Microaerobic Metabolic Activity, Abscess Formation, and Survival in Macrophages
Microbiology Spectrum
NAD+-dependent malolactic enzyme coding gene (mleS)
Staphylococcus aureus
macrophage survival
metabolism
mouse skin abscess
title mleS in Staphylococcus aureus Contributes to Microaerobic Metabolic Activity, Abscess Formation, and Survival in Macrophages
title_full mleS in Staphylococcus aureus Contributes to Microaerobic Metabolic Activity, Abscess Formation, and Survival in Macrophages
title_fullStr mleS in Staphylococcus aureus Contributes to Microaerobic Metabolic Activity, Abscess Formation, and Survival in Macrophages
title_full_unstemmed mleS in Staphylococcus aureus Contributes to Microaerobic Metabolic Activity, Abscess Formation, and Survival in Macrophages
title_short mleS in Staphylococcus aureus Contributes to Microaerobic Metabolic Activity, Abscess Formation, and Survival in Macrophages
title_sort mles in staphylococcus aureus contributes to microaerobic metabolic activity abscess formation and survival in macrophages
topic NAD+-dependent malolactic enzyme coding gene (mleS)
Staphylococcus aureus
macrophage survival
metabolism
mouse skin abscess
url https://journals.asm.org/doi/10.1128/spectrum.00909-23
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