MtrA Response Regulator Controls Cell Division and Cell Wall Metabolism and Affects Susceptibility of Mycobacteria to the First Line Antituberculosis Drugs

Gorla, Purushotham; Plocinska, Renata; Sarva, Krishna; Satsangi, Akash Tripathi; Paul, Pandeeti Emmanuel Vijay; Donnelly, Robert; Dziadek, Jarosław; Rajagopalan, Malini; Madiraju, Murty V. V. S.

doi:10.3389/fmicb.2018.02839

Cited by 44 publications

(72 citation statements)

References 61 publications

(129 reference statements)

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“…However, MtrA also binds and activates the iniBAC promoter, an operon encoding an efflux pump that increases resistance to isoniazid and ethambutol, two first-line antituberculosis drugs [143][144][145][247][248][249][250][251][252][253]. Additionally, mutations to mtrA in M. smegmatis resulted in decreased resistance to rifampicin and vancomycin, albeit with increased resistance to isoniazid [254]. In the opportunistic pathogen M. avium, MtrAB is required for conversion to a virulent, MDR colony morphotype, presumably by decreasing cell permeability [146].…”

Section: Mycobacteriamentioning

confidence: 99%

Roles of Two-Component Regulatory Systems in Antibiotic Resistance

2019

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Two-component regulatory systems (TCSs) are a major mechanism by which bacteria sense and respond to changes in their environment. TCSs typically consist of two proteins that bring about major regulation of the cell genome through coordinated action mediated by phosphorylation. Environmental conditions that activate TCSs are numerous and diverse and include exposure to antibiotics as well as conditions inside a host. The resulting regulatory action often involves activation of antibiotic defenses and changes to cell physiology that increase antibiotic resistance. Examples of resistance mechanisms enacted by TCSs contained in this review span those found in both Gram-negative and Gram-positive species and include cell surface modifications, changes in cell permeability, increased biofilm formation, and upregulation of antibiotic-degrading enzymes.

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Section: Mycobacteriamentioning

confidence: 99%

Roles of Two-Component Regulatory Systems in Antibiotic Resistance

2019

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“…To determine the possible binding of thio-disaccharide to PPE51, the protein was expressed in E. coli and purified by affinity chromatography, as described in Methods (Supplementary Figure S1). Recombinant PPE51, as well as PPE51-carrying MBP-domain and the NAD-dependent DNA ligase 6His-LigA [45], the protein involved in the DNA replication process, and MBP-MtrA [49] response regulator, were used as a coating experimental and control proteins, respectively, in binding experiments with 5 µCi (1 µg) of tritium-labeled thio-disaccharide ([ 3 H]T-6). The intensity of T-6 binding was measured by liquid scintillation counting ( Figure 1B) and was finally calculated by subtracting the average CPM estimated for proteins incubated without labeled T-6 from the CPM determined for the homologous protein (experimental or control) incubated with [ 3 H]T-6.…”

Section: Ppe51 Binds To T-6mentioning

confidence: 99%

PPE51 Is Involved in the Uptake of Disaccharides by Mycobacterium tuberculosis

Korycka-Machała

Pawełczyk

Borówka

et al. 2020

Cells

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We have recently found that selected thio-disaccharides possess bactericidal effects against Mycobacterium tuberculosis but not against Escherichia coli or Staphylococcus aureus. Here, we selected spontaneous mutants displaying resistance against the investigated thio-glycoside. According to next-generation sequencing, four of six analyzed mutants which were resistant to high concentrations of the tested chemical carried nonsynonymous mutations in the gene encoding the PPE51 protein. The complementation of these mutants with an intact ppe51 gene returned their sensitivity to the wild-type level. The uptake of tritiated thio-glycoside was significantly more abundant in wild-type Mycobacterium tuberculosis compared to the strain carrying the mutated ppe51 gene. The ppe51 mutations or CRISPR-Cas9-mediated downregulation of PPE51 expression affected the growth of mutant strains on minimal media supplemented with disaccharides (maltose or lactose) but not with glycerol or glucose as the sole carbon and energy source. Taking the above into account, we postulate that PPE51 participates in the uptake of disaccharides by tubercle bacilli.

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“…WH15, we similarly observed a protein similar to the copper-exporting P-type ATPase and cation/multidrug efflux pump AdeG, which could be involved in maintaining optimal levels of Mn inside the bacterial cell. Furthermore, we found a protein similar to RcnB/YohN, which is an essential protein for Ni/Co homeostasis in E. coli (Bleriot et al, 2011), and a protein similar to gene MtrA, which is involved in cell division control and cell wall metabolism in Mycobacterium tuberculosis (Gorla et al, 2018).…”

Section: Discussionmentioning

confidence: 80%

Impact of Different Trace Elements on the Growth and Proteome of Two Strains of Granulicella, Class “Acidobacteriia”

et al. 2020

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Acidobacteria represents one of the most dominant bacterial groups across diverse ecosystems. However, insight into their ecology and physiology has been hampered by difficulties in cultivating members of this phylum. Previous cultivation efforts have suggested an important role of trace elements for the proliferation of Acidobacteria, however, the impact of these metals on their growth and metabolism is not known. In order to gain insight into this relationship, we evaluated the effect of trace element solution SL10 on the growth of two strains (5B5 and WH15) of Acidobacteria belonging to the genus Granulicella and studied the proteomic responses to manganese (Mn). Granulicella species had highest growth with the addition of Mn, as well as higher tolerance to this metal compared to seven other metal salts. Variations in tolerance to metal salt concentrations suggests that Granulicella sp. strains possess different mechanisms to deal with metal ion homeostasis and stress. Furthermore, Granulicella sp. 5B5 might be more adapted to survive in an environment with higher concentration of several metal ions when compared to Granulicella sp. WH15. The proteomic profiles of both strains indicated that Mn was more important in enhancing enzymatic activity than to protein expression regulation. In the genomic analyses, we did not find the most common transcriptional regulation of Mn homeostasis, but we found candidate transporters that could be potentially involved in Mn homeostasis for Granulicella species. The presence of such transporters might be involved in tolerance to higher Mn concentrations, improving the adaptability of bacteria to metal enriched environments, such as the decaying wood-rich Mn environment from which these two Granulicella strains were isolated.

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MtrA Response Regulator Controls Cell Division and Cell Wall Metabolism and Affects Susceptibility of Mycobacteria to the First Line Antituberculosis Drugs

Cited by 44 publications

References 61 publications

Roles of Two-Component Regulatory Systems in Antibiotic Resistance

Roles of Two-Component Regulatory Systems in Antibiotic Resistance

PPE51 Is Involved in the Uptake of Disaccharides by Mycobacterium tuberculosis

Impact of Different Trace Elements on the Growth and Proteome of Two Strains of Granulicella, Class “Acidobacteriia”

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