ppat.1012050.g002.tif (275.76 kB)

Prevalence of various LldD2 mutations.

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posted on 2024-02-29, 18:55 authored by Sydney Stanley, Xin Wang, Qingyun Liu, Young Yon Kwon, Abigail M. Frey, Nathan D. Hicks, Andrew J. Vickers, Sheng Hui, Sarah M. Fortune

(A) Schematic of LldD2 depicting the amino acid position of coding mutations listed in Fig 1. The purple rectangle illustrates the FMN-dependent alpha-hydroxy acid dehydrogenase motif. (B) Percentage of lldD2 homoplastic or clade-defining mutations belonging to the indicated genotype. 17,148 mutations spanning 216 unique loci were identified across 50,270 strains. (C) Percentage of strains carrying at least one of the indicated mutations in either LldD1 or LldD2. (D) Comparison of the percentage of strains carrying at least one LldD1 or LldD2 mutation for each lineage.

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providing experimental evidence div >< p central carbon metabolism 1 virulence system mycobacterium tuberculosis discernible growth defect dependent antibiotic susceptibility mutations functionally increase human host environment global clinical isolates lactate dehydrogenase reveals assessing mtb genes 13 clinical isolates vivo mtb growth lactate dehydrogenase intracellular environment host pressure genes involved dependent l variation across transcriptionally sensitive sugar phosphates strongest targets stepwise nature selective advantage salient feature robust incorporation provides context pressures facing poorly characterized pleiotropic effects mycobacterial cell multifunctional role mtb genome lldd2 lactate accumulation functional reporter detoxification benefit deleterious buildup defining mutations data illustrate bacterial determinants bacterial adaption ancestral lineage

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