The MarR family transcription factor Rv1404 coordinates adaptation of Mycobacterium tuberculosis to acid stress via controlled expression of Rv1405c, a virulence-associated methyltransferase

Healy, Claire; Golby, Paul; MacHugh, David E.; Gordon, Stephen V.

doi:10.1016/j.tube.2015.10.003

Cited by 32 publications

(27 citation statements)

References 22 publications

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“…Genetic screening suggests that pagO in LA-Kp may be required for liver abscess induction in a mouse model (Tu et al, 2009). SAM-dependent methyltransferase has been reported to play an important role in the adaptation to hostile environment of the macrophage and acid stress in Mycobacterium tuberculosis (Healy et al, 2016). shiF has been speculated as an auxiliary gene that promotes the transport of lysine, the precursor of aerobactin ( iucABCD ) in E. coli .…”

Section: Resultsmentioning

confidence: 99%

Clinical and Genomic Analysis of Liver Abscess-Causing Klebsiella pneumoniae Identifies New Liver Abscess-Associated Virulence Genes

Jiang

et al. 2016

Front. Cell. Infect. Microbiol.

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Hypervirulent variants of Klebsiella pneumoniae (hvKp) that cause invasive community-acquired pyogenic liver abscess (PLA) have emerged globally. Little is known about the virulence determinants associated with hvKp, except for the virulence genes rmpA/A2 and siderophores (iroBCD/iucABCD) carried by the pK2044-like large virulence plasmid. Here, we collected most recent clinical isolates of hvKp from PLA samples in China, and performed clinical, molecular, and genomic sequencing analyses. We found that 90.9% (40/44) of the pathogens causing PLA were K. pneumoniae. Among the 40 LA-Kp, K1 (62.5%), and K2 (17.5%) were the dominant serotypes, and ST23 (47.5%) was the major sequence type. S1-PFGE analyses demonstrated that although 77.5% (31/40) of the LA-Kp isolates harbored a single large virulence plasmid varied in size, 5 (12.5%) isolates had no plasmid and 4 (10%) had two or three plasmids. Whole genome sequencing and comparative analysis of 3 LA-Kp and 3 non-LA-Kp identified 133 genes present only in LA-Kp. Further, large scale screening of the 133 genes in 45 LA-Kp and 103 non-LA-Kp genome sequences from public databases identified 30 genes that were highly associated with LA-Kp, including iroBCD, iucABCD and rmpA/A2 and 21 new genes. Then, these 21 new genes were analyzed in 40 LA-Kp and 86 non-LA-Kp clinical isolates collected in this study by PCR, showing that new genes were present 80–100% among LA-Kp isolates while 2–11% in K. pneumoniae isolates from sputum and urine. Several of the 21 genes have been proposed as virulence factors in other bacteria, such as the gene encoding SAM-dependent methyltransferase and pagO which protects bacteria from phagocytosis. Taken together, these genes are likely new virulence factors contributing to the hypervirulence phenotype of hvKp, and may deepen our understanding of virulence mechanism of hvKp.

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Section: Resultsmentioning

confidence: 99%

Clinical and Genomic Analysis of Liver Abscess-Causing Klebsiella pneumoniae Identifies New Liver Abscess-Associated Virulence Genes

Jiang

et al. 2016

Front. Cell. Infect. Microbiol.

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“…For example, exposure to hydrogen peroxide or nitric oxide led to dissociation of MosR from DNA and subsequent upregulation of the putative oxidoreductase Rv1050 (38). Rv1404 was involved in Mtb's response to acid and hypoxia by up-regulating 10 genes, including two putative methyl transferases, Rv1403c and Rv1405c (39).…”

Section: Discussionmentioning

confidence: 99%

N -methylation of a bactericidal compound as a resistance mechanism in Mycobacterium tuberculosis

Warrier

Kapilashrami

Argyrou

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The rising incidence of antimicrobial resistance (AMR) makes it imperative to understand the underlying mechanisms. Mycobacterium tuberculosis (Mtb) is the single leading cause of death from a bacterial pathogen and estimated to be the leading cause of death from AMR. A pyrido-benzimidazole, 14, was reported to have potent bactericidal activity against Mtb. Here, we isolated multiple Mtb clones resistant to 14. Each had mutations in the putative DNA-binding and dimerization domains of rv2887, a gene encoding a transcriptional repressor of the MarR family. The mutations in Rv2887 led to markedly increased expression of rv0560c. We characterized Rv0560c as an S-adenosyl-L-methionine-dependent methyltransferase that N-methylates 14, abolishing its mycobactericidal activity. An Mtb strain lacking rv0560c became resistant to 14 by mutating decaprenylphosphoryl-β-d-ribose 2-oxidase (DprE1), an essential enzyme in arabinogalactan synthesis; 14 proved to be a nanomolar inhibitor of DprE1, and methylation of 14 by Rv0560c abrogated this activity. Thus, 14 joins a growing list of DprE1 inhibitors that are potently mycobactericidal. Bacterial methylation of an antibacterial agent, 14, catalyzed by Rv0560c of Mtb, is a previously unreported mechanism of AMR.

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“…Hydrolase (Peptidase family S58) Rv1338 murI Glutamate racemase Essential component peptidoglycan Rv1405c SAM-dependent methlytransferase 51 Controlled by transcriptional regulator MarR to counter acid stress; upregulated during enduring hypoxic response Rv1410c…”

Section: Rv0099 Fadd10mentioning

confidence: 99%

Microbial Offense vs Host Defense: Who Controls the TB Granuloma?

Martinot

2017

Vet Pathol

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The granuloma is the hallmark of tuberculosis and simultaneously signifies acquisition of an infection and induction of a host immune response. But who benefits more from the development of the granuloma, the host or the pathogen? Is microbe or man dictating disease course and progression? Mycobacterial diseases affect humans and animals alike, and the concepts presented in this review reflect host-pathogen interactions that influence not only mycobacterial granulomas in humans and animals but also other infectious granulomatous diseases that are encountered in veterinary medicine. Current dogma supports that an organized granuloma is a mark of an adequate and "restrictive" host immune response. However, the formation of a granuloma also provides a niche for the maturation, growth, and persistence of numerous infectious agents, and these pathogens devote some portion of their genetic machinery to ensuring these structures' form. An understanding of pathogens' contributions to granuloma formation can aid the development of host-directed therapies and other antimicrobial and antiparasitic therapies that can tip this balance in favor of a restrictive host response and elimination-not just containment-of the infectious organism. This review discusses animal models that have aided our understanding of pathogens' contribution to the host response and how mycobacterial virulence genes direct host pathology in ways that may aid disease transmission and/or persistence in the form of latent infection.

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The MarR family transcription factor Rv1404 coordinates adaptation of Mycobacterium tuberculosis to acid stress via controlled expression of Rv1405c, a virulence-associated methyltransferase

Cited by 32 publications

References 22 publications

Clinical and Genomic Analysis of Liver Abscess-Causing Klebsiella pneumoniae Identifies New Liver Abscess-Associated Virulence Genes

Clinical and Genomic Analysis of Liver Abscess-Causing Klebsiella pneumoniae Identifies New Liver Abscess-Associated Virulence Genes

N -methylation of a bactericidal compound as a resistance mechanism in Mycobacterium tuberculosis

Microbial Offense vs Host Defense: Who Controls the TB Granuloma?

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