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• W4220752476 abstract "Bacillus anthracis, the anthrax agent, exhibits robust proliferation in diverse niches of mammalian hosts. The metabolic attributes of B. anthracis that permit rapid growth in multiple mammalian tissues have not been established. We posit that branched-chain amino acid (BCAA) (isoleucine, leucine, and valine) metabolism is key to B. anthracis pathogenesis. Increasing evidence indicates the relationships between B. anthracis virulence and the expression of BCAA-related genes. The expression of some BCAA-related genes is altered during culture in bovine blood in vitro, and the bacterium exhibits valine auxotrophy in a blood serum mimic medium. Transcriptome analyses have revealed that the virulence regulator AtxA, which positively affects the expression of the anthrax toxin and capsule genes, negatively regulates genes predicted to be associated with BCAA biosynthesis and transport. Here, we show that B. anthracis growth in defined medium is severely restricted in the absence of exogenous BCAAs, indicating that BCAA transport is required for optimal growth in vitro. We demonstrate functional redundancy among multiple BrnQ-type BCAA transporters. Three transporters are associated with isoleucine and valine transport, and the deletion of one, BrnQ3, attenuates virulence in a murine model for anthrax. Interestingly, an ilvD-null mutant lacking dihydroxy acid dehydratase, an enzyme essential for BCAA synthesis, exhibits unperturbed growth when cultured in medium containing BCAAs but is highly attenuated in the murine model. Finally, our data show that BCAAs enhance AtxA activity in a dose-dependent manner, suggesting a model in which BCAAs serve as a signal for virulence gene expression. IMPORTANCE Infection with B. anthracis can result in systemic disease with large numbers of the bacterium in multiple tissues. We found that branched-chain amino acid (BCAA) synthesis is insufficient for the robust growth of B. anthracis; access to BCAAs is necessary for the proliferation of the pathogen during culture and during infection in a murine model for anthrax. B. anthracis produces an unusually large repertoire of BCAA-related transporters. We identified three isoleucine/valine transporters with partial functional redundancy during culture. The deletion of one of these transporters, BrnQ3, resulted in attenuated virulence. Interestingly, a BCAA biosynthesis mutant grew well in medium containing BCAAs but, like BrnQ3, was attenuated for virulence. These results suggest that BCAAs are limiting in multiple niches during infection and further our understanding of the nutritional requirements of this important pathogen." @default.
• W4220752476 created "2022-04-03" @default.
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• W4220752476 date "2022-02-22" @default.
• W4220752476 modified "2023-09-25" @default.
• W4220752476 title "BrnQ-Type Branched-Chain Amino Acid Transporters Influence Bacillus anthracis Growth and Virulence" @default.
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• W4220752476 cites W1572022498 @default.
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• W4220752476 cites W1587381346 @default.
• W4220752476 cites W1805247260 @default.
• W4220752476 cites W1840588602 @default.
• W4220752476 cites W1862273946 @default.
• W4220752476 cites W1943327251 @default.
• W4220752476 cites W1957227160 @default.
• W4220752476 cites W1963563104 @default.
• W4220752476 cites W1965462834 @default.
• W4220752476 cites W1972864050 @default.
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• W4220752476 cites W1998591058 @default.
• W4220752476 cites W2000601745 @default.
• W4220752476 cites W2006368907 @default.
• W4220752476 cites W2009751240 @default.
• W4220752476 cites W2014699742 @default.
• W4220752476 cites W2028268916 @default.
• W4220752476 cites W2028375941 @default.
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• W4220752476 cites W2060913542 @default.
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• W4220752476 cites W2074060378 @default.
• W4220752476 cites W2078505996 @default.
• W4220752476 cites W2081692326 @default.
• W4220752476 cites W2093784289 @default.
• W4220752476 cites W2099540110 @default.
• W4220752476 cites W2101047480 @default.
• W4220752476 cites W2108604935 @default.
• W4220752476 cites W2112019129 @default.
• W4220752476 cites W2116919597 @default.
• W4220752476 cites W2124325139 @default.
• W4220752476 cites W2130641564 @default.
• W4220752476 cites W2142237413 @default.
• W4220752476 cites W2144645983 @default.
• W4220752476 cites W2147324295 @default.
• W4220752476 cites W2148865961 @default.
• W4220752476 cites W2150050125 @default.
• W4220752476 cites W2150577180 @default.
• W4220752476 cites W2151401294 @default.
• W4220752476 cites W2152053669 @default.
• W4220752476 cites W2158521027 @default.
• W4220752476 cites W2162915355 @default.
• W4220752476 cites W2163837366 @default.
• W4220752476 cites W2165787676 @default.
• W4220752476 cites W2167268416 @default.
• W4220752476 cites W2169660828 @default.
• W4220752476 cites W2296691750 @default.
• W4220752476 cites W2517554512 @default.
• W4220752476 cites W2524908713 @default.
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• W4220752476 doi "https://doi.org/10.1128/mbio.03640-21" @default.
• W4220752476 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35073743" @default.
• W4220752476 hasPublicationYear "2022" @default.
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