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- Repeated Exposure of Vancomycin to Vancomycin-Susceptible Staphylococcus aureus (VSSA) Parent Emerged VISA and VRSA Strains with Enhanced Virulence Potentials.
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An Nguyen, J Jean Sophy Roy, Ji-Hoon Kim, Kyung-Hee Yun, Wonsik Lee, Kyeong Kyu Kim, Truc Kim, Akhilesh Kumar Chaurasia
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J. Microbiol. 2024;62(7):535-553. Published online May 30, 2024
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DOI: https://doi.org/10.1007/s12275-024-00139-8
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Abstract
- The emergence of resistance against the last-resort antibiotic vancomycin in staphylococcal infections is a serious concern for human health. Although various drug-resistant pathogens of diverse genetic backgrounds show higher virulence potential, the underlying mechanism behind this is not yet clear due to variability in their genetic dispositions. In this study, we investigated the correlation between resistance and virulence in adaptively evolved isogenic strains. The vancomycin-susceptible Staphylococcus aureus USA300 was exposed to various concentrations of vancomycin repeatedly as a mimic of the clinical regimen to obtain mutation(s)-accrued-clonally-selected (MACS) strains. The phenotypic analyses followed by expression of the representative genes responsible for virulence and resistance of MACS strains were investigated. MACS strains obtained under 2 and 8 µg/ml vancomycin, named Van2 and Van8, respectively; showed enhanced vancomycin minimal inhibitory concentrations (MIC) to 4 and 16 µg/ml, respectively. The cell adhesion and invasion of MACS strains increased in proportion to their MICs. The correlation between resistance and virulence potential was partially explained by the differential expression of genes known to be involved in both virulence and resistance in MACS strains compared to parent S. aureus USA300. Repeated treatment of vancomycin against vancomycin-susceptible S. aureus (VSSA) leads to the emergence of vancomycin-resistant strains with variable levels of enhanced virulence potentials.
- Cytophaga hutchinsonii chu_2177, encoding the O-antigen ligase, is essential for cellulose degradation
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Yahong Tan , Wenxia Song , Lijuan Gao , Weican Zhang , Xuemei Lu
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J. Microbiol. 2022;60(4):364-374. Published online January 7, 2022
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DOI: https://doi.org/10.1007/s12275-022-1531-3
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Abstract
- Cytophaga hutchinsonii can efficiently degrade crystalline
cellulose, in which the cell surface cellulases secreted by the
type IX secretion system (T9SS) play important roles, but
the degradation mechanism remains unclear, and the anchor
mechanism of cellulases on the outer membrane in C.
hutchinsonii has not been studied. Here, chu_2177 was identified
by transposon mutagenesis and was proved to be indispensable
for cellulose utilization in C. hutchinsonii. Disruption
of chu_2177 resulted in O-antigen deficiency and chu_
177 could confer O-antigen ligase activity upon an Escherichia
coli waal mutant, indicating that chu_2177 encoded the Ontigen
ligase. Moreover, deletion of chu_2177 caused defects
in cellulose utilization, cell motility, biofilm formation, and
stress resistance. Further study showed that the endoglucanase
activity was markedly decreased in the outer membrane
but was increased in the culture fluid without chu_2177.
Western blot proved that endoglucanase CHU_1336 was not
located on the outer membrane but was released in the culture
fluid of the Δ2177 mutant. Further proteomics analysis
showed that many cargo proteins of T9SS were missing in
the outer membrane of the Δ2177 mutant. Our study revealed
that the deletion of chu_2177 affected the localization of
many T9SS cargo proteins including cellulases on the outer
membrane of C. hutchinsonii.
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