Mycobacterial MazG Is a Novel NTP Pyrophosphohydrolase Involved in Oxidative Stress Response

Lu, Liangdong; Sun, Qing; Fan, Xiao‐Yong; Zhong, Yi; Yao, Yufeng; Zhao, Guoping

doi:10.1074/jbc.m109.088872

Cited by 48 publications

(55 citation statements)

References 38 publications

(63 reference statements)

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“…The species of the MTBC that DS6A is known to infect (M. tuberculosis, M. bovis, M. canettii, M. microti, and M. africanum) grow slowly, with doubling times of at least 16 h. The presence of MazG, a nucleoside triphosphate pyrophosphohydrolase known to upregulate the host metabolism (42), was also thought to be required by DS6A for efficient propagation and to serve the need to propagate faster than the division time of M. tuberculosis. Surprisingly, the presence and absence of mazG in ⌽ 2 GFP12 and ⌽ 2 GFP13, respectively, did not affect fitness, and both phages generated titers comparable to that of wild-type DS6A.…”

Section: Discussionmentioning

confidence: 99%

Fluorescent Reporter DS6A Mycobacteriophages Reveal Unique Variations in Infectibility and Phage Production in Mycobacteria

et al. 2016

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Mycobacteriophage DS6A is unique among the more than 8,000 isolated mycobacteriophages due to its ability to form plaques exclusively on mycobacteria belonging to the Mycobacterium tuberculosis complex (MTBC). Speculation surrounding this specificity has led to unsupported assertions in published studies and patents that nontuberculous mycobacteria (NTM) are wholly resistant to DS6A infection. In this study, we identified two independent nonessential regions in the DS6A genome and replaced them with an mVenus-expressing plasmid to generate fluorescent reporter phages ⌽ 2 GFP12 and ⌽ 2 GFP13. We show that even though DS6A is able to form plaques only on MTBC bacteria, infection of various NTM results in mVenus expression in transduced cells. The efficiency of DS6A in delivering DNA varied between NTM species. Additionally, we saw a striking difference in the efficiency of DNA delivery between the closely related members of the Mycobacterium abscessus complex, M. abscessus and Mycobacterium massiliense. We also demonstrated that TM4 and DS6A, two phages that do not form plaques on M. massiliense, differ in their ability to deliver DNA, suggesting that there is a phage-specific restriction between mycobacterial species. Phylogenetic analysis reveals that the DS6A genome has a characteristically mosaic structure but provided few insights into the basis for the specificity for MTBC hosts. This study demonstrates that the inability of the MTBC-specific phage DS6A to form plaques on NTM is more complex than previously thought. Moreover, the DS6A-derived fluorophages provide important new tools for the study of mycobacterial biology. IMPORTANCEThe coevolution of bacteria and their infecting phages involves a constant arms race for bacteria to prevent phage infection and phage to overcome these preventions. Although a diverse array of phage defense systems is well characterized in bacteria, very few phage restriction systems are known in mycobacteria. The DS6A mycobacteriophage is unique in the mycobacterial world in that it forms plaques only on members of the Mycobacterium tuberculosis complex. However, the novel DS6A reporter phages developed in this work demonstrate that DS6A can infect nontuberculous mycobacteria at various efficiencies. By comparing the abilities of DS6A and another phage, TM4, to infect and form plaques on various mycobacterial species, we can begin to discern new phage restriction systems employed within the genus. The standard treatment for a drug-susceptible Mycobacterium tuberculosis infection is four drugs (rifampin, isoniazid, pyrazinamide, and ethambutol) for 2 months, followed by 4 months of two drugs (rifampin and isoniazid). One of the key aspects of successfully treating tuberculosis is ensuring that the infecting strain is susceptible to each of the antibiotics given; therefore, quickly diagnosing antibiotic resistance is important for successful patient outcome as well as for lowering the incidence of the generation of drug-resistant mutants from improper antibiotic administra...

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Section: Discussionmentioning

confidence: 99%

Fluorescent Reporter DS6A Mycobacteriophages Reveal Unique Variations in Infectibility and Phage Production in Mycobacteria

et al. 2016

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“…Many marine phages have proteins containing MazG domains, suggesting the importance of this domain in the proliferation of marine phages (44)(45)(46). In bacteria, MazG domain proteins have been shown to function in stress responses or removal of noncanonical nucleotides (47)(48)(49). It has been suggested that phage MazG proteins may contribute to phage propagation by helping sustain the metabolism of starved host bacteria (44,46).…”

Section: Resultsmentioning

confidence: 99%

Genome of a SAR116 bacteriophage shows the prevalence of this phage type in the oceans

Kang

et al. 2013

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

122

133

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The abundance, genetic diversity, and crucial ecological and evolutionary roles of marine phages have prompted a large number of metagenomic studies. However, obtaining a thorough understanding of marine phages has been hampered by the low number of phage isolates infecting major bacterial groups other than cyanophages and pelagiphages. Therefore, there is an urgent requirement for the isolation of phages that infect abundant marine bacterial groups. In this study, we isolated and characterized HMO-2011, a phage infecting a bacterium of the SAR116 clade, one of the most abundant marine bacterial lineages. HMO-2011, which infects “ Candidatus Puniceispirillum marinum” strain IMCC1322, has an ∼55-kb dsDNA genome that harbors many genes with novel features rarely found in cultured organisms, including genes encoding a DNA polymerase with a partial DnaJ central domain and an atypical methanesulfonate monooxygenase. Furthermore, homologs of nearly all HMO-2011 genes were predominantly found in marine metagenomes rather than cultured organisms, suggesting the novelty of HMO-2011 and the prevalence of this phage type in the oceans. A significant number of the viral metagenome sequences obtained from the ocean surface were best assigned to the HMO-2011 genome. The number of reads assigned to HMO-2011 accounted for 10.3%–25.3% of the total reads assigned to viruses in seven viromes from the Pacific and Indian Oceans, making the HMO-2011 genome the most or second-most frequently assigned viral genome. Given its ability to infect the abundant SAR116 clade and its widespread distribution, Puniceispirillum phage HMO-2011 could be an important resource for marine virus research.

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“…5 deduced amino acid sequences shared 46-52 % amino acid sequence identity with the virion proteins of PaMx42. (Gross et al, 2006;Lu et al, 2010). Under stress conditions, unusual nucleotides begin to accumulate in the cell, facilitating the programmed cell death.…”

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confidence: 99%

Comparative analysis of two bacteriophages of Xanthomonas arboricola pv. juglandis

Dömötör

Frank

Rákhely

et al. 2016

Infection, Genetics and Evolution

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Mycobacterial MazG Is a Novel NTP Pyrophosphohydrolase Involved in Oxidative Stress Response

Cited by 48 publications

References 38 publications

Fluorescent Reporter DS6A Mycobacteriophages Reveal Unique Variations in Infectibility and Phage Production in Mycobacteria

Fluorescent Reporter DS6A Mycobacteriophages Reveal Unique Variations in Infectibility and Phage Production in Mycobacteria

Genome of a SAR116 bacteriophage shows the prevalence of this phage type in the oceans

Comparative analysis of two bacteriophages of Xanthomonas arboricola pv. juglandis

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