Dataset Information

Mab_3083c Is a Homologue of RNase J and Plays a Role in Colony Morphotype, Aggregation, and Sliding Motility of Mycobacterium abscessus.

ABSTRACT: Mycobacterium abscessus is an opportunistic pathogen causing human diseases, especially in immunocompromised patients. M. abscessus strains with a rough morphotype are more virulent than those with a smooth morphotype. Morphotype switch may occur during a clinical infection. To investigate the genes involved in colony morphotype switching, we performed transposon mutagenesis in a rough clinical strain of M. abscessus. A morphotype switching mutant (smooth) named mab_3083c::Tn was obtained. This mutant was found to have a lower aggregative ability and a higher sliding motility than the wild type strain. However, its glycopeptidolipid (GPL) content remained the same as those of the wild type. Complementation of the mutant with a functional mab_3083c gene reverted its morphotype back to rough, indicating that mab_3083c is associated with colony morphology of M. abscessus. Bioinformatic analyses showed that mab_3083c has a 75.4% identity in amino acid sequence with the well-characterized ribonuclease J (RNase J) of M. smegmatis (RNase JMsmeg). Complementation of the mutant with the RNase J gene of M. smegmatis also switched its colony morphology from smooth back to rough. These results suggest that Mab_3083c is a homologue of RNase J and involved in regulating M. abscessus colony morphotype switching.

SUBMITTER: Liu TY

PROVIDER: S-EPMC8064342 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Mab_3083c Is a Homologue of RNase J and Plays a Role in Colony Morphotype, Aggregation, and Sliding Motility of Mycobacterium abscessus.

Liu Ting-Yu TY Tsai Sheng-Hui SH Chen Jenn-Wei JW Wang Yu-Ching YC Hu Shiau-Ting ST Chen Yih-Yuan YY

Microorganisms 20210325 4

Mycobacterium abscessus is an opportunistic pathogen causing human diseases, especially in immunocompromised patients. M. abscessus strains with a rough morphotype are more virulent than those with a smooth morphotype. Morphotype switch may occur during a clinical infection. To investigate the genes involved in colony morphotype switching, we performed transposon mutagenesis in a rough clinical strain of M. abscessus. A morphotype switching mutant (smooth) named mab_3083c ...[more]

PMID: 33805851

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Project description:Mycobacterium abscessus is an opportunistic pathogen whose treatment is confounded by widespread multidrug resistance. The therapeutic use of bacteriophages against Mycobacterium abscessus infections offers a potential alternative approach, although the spectrum of phage susceptibilities among M. abscessus isolates is not known. We determined the phage infection profiles of 82 M. abscessus recent clinical isolates and find that colony morphotype-rough or smooth-is a key indicator of phage susceptibility. None of the smooth strains are efficiently killed by any phages, whereas 80% of rough strains are infected and efficiently killed by at least one phage. The repertoire of phages available for potential therapy of rough morphotype infections includes those with relatively broad host ranges, host range mutants of Mycobacterium smegmatis phages, and lytically propagated viruses derived from integrated prophages. The rough colony morphotype results from indels in the glycopeptidolipid synthesis genes mps1 and mps2, negating reversion to smooth as a common route to phage resistance. Resistance is thus rare, and although mutations in polyketide synthesis, uvrD2, and rpoZ can confer resistance, these likely also impair survival in vivo The expanded therapeutic repertoire and the resistance profiles show that small cocktails or single phages could be suitable for controlling infections with rough strains.IMPORTANCEMycobacterium abscessus infections in cystic fibrosis patients are challenging to treat due to widespread antibiotic resistance. The therapeutic use of lytic bacteriophages presents a new potential strategy, but the great variation among clinical M. abscessus isolates demands determination of phage susceptibility prior to therapy. Elucidation of the variation in phage infection and factors determining it, expansion of the suite of therapeutic phage candidates, and a greater understanding of phage resistance mechanisms substantially advances the potential for broad implementation of new therapeutic options for M. abscessus infections.

Project description:Competitive interactions mediated by released chemicals (e.g., toxins) are prominent in multispecies communities, but the effects of these chemicals at subinhibitory concentrations on susceptible bacteria are poorly understood. Although Pseudomonas aeruginosa and species of the Burkholderia cepacia complex (Bcc) can exist together as a coinfection in cystic fibrosis airways, P. aeruginosa toxins can kill Bcc species in vitro Consequently, these bacteria become an ideal in vitro model system to study the impact of sublethal levels of toxins on the biology of typical susceptible bacteria, such as the Bcc, when exposed to P. aeruginosa toxins. Using P. aeruginosa spent medium as a source of toxins, we showed that a small window of subinhibitory concentrations modulated the colony morphotype and swarming motility of some but not all tested Bcc strains, for which rhamnolipids were identified as the active molecule. Using a random transposon mutagenesis approach, we identified several genes required by the Bcc to respond to low concentrations of rhamnolipids and consequently affect the ability of this microbe to change its morphotype and swarm over surfaces. Among those genes identified were those coding for type IVb-Tad pili, which are often required for virulence in various bacterial pathogens. Our study demonstrates that manipulating chemical gradients in vitro can lead to the identification of bacterial behaviors relevant to polymicrobial infections.IMPORTANCE Interspecies interactions can have profound effects on the development and outcomes of polymicrobial infections. Consequently, improving the molecular understanding of these interactions could provide us with new insights on the possible long-term consequences of these chronic infections. In this study, we show that P. aeruginosa-derived rhamnolipids, which participate in Bcc killing at high concentrations, can also trigger biological responses in Burkholderia spp. at low concentrations. The modulation of potential virulence phenotypes in the Bcc by P. aeruginosa suggests that these interactions contribute to pathogenesis and disease severity in the context of polymicrobial infections.

Dataset Information

Mab_3083c Is a Homologue of RNase J and Plays a Role in Colony Morphotype, Aggregation, and Sliding Motility of Mycobacterium abscessus.

Publications

<i>Mab_3083c</i> Is a Homologue of RNase J and Plays a Role in Colony Morphotype, Aggregation, and Sliding Motility of <i>Mycobacterium abscessus</i>.

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