GP30 of the mycobacteriophage CASbig impairs mycobacterial adaptation during acidic stress and in macrophages

The rapid emergence of multidrug-resistant and extensively drug-resistant Tuberculosis retrieved intense interest in phage-based therapy. This old approach, which was abandoned in the west in the 1940s but is generating renewed interest, has stimulated fresh research on mycobacteriophages and their lytic efficiency against their hosts. GP30 is a novel protein of the mycobacteriophage CASbig with undiscovered function. In this study, we analyzed the role of CASbig gp30 in the host Mycobacterium smegmatis. Overexpression of gp30 in the host led to reduced growth in acidic medium and attenuated the intracellular survival rate of M. smegmatis inside the THP-1 macrophages, which may be linked to the altered lipid profile of the recombinant bacterial cell wall. In a word, this study suggested that gp30, a novel gene from a mycobacteriophage, modulated lipid composition and content to hamper the survivability of bacteria under stress conditions.

[1]  M. Puiu,et al.  Bacteriophage gene products as potential antimicrobials against tuberculosis. , 2019, Biochemical Society transactions.

[2]  Hailong Yang,et al.  A small mycobacteriophage-derived peptide and its improved isomer restrict mycobacterial infection via dual mycobactericidal-immunoregulatory activities , 2019, The Journal of Biological Chemistry.

[3]  S. S. Karade,et al.  Rv3272 encodes a novel Family III CoA transferase that alters the cell wall lipid profile and protects mycobacteria from acidic and oxidative stress. , 2019, Biochimica et biophysica acta. Proteins and proteomics.

[4]  J. Pedrosa,et al.  Antimicrobial activity of Mycobacteriophage D29 Lysin B during Mycobacterium ulcerans infection , 2018, bioRxiv.

[5]  Wu Li,et al.  The Mycobacterium tuberculosis protein Rv2387 is involved in cell wall remodeling and susceptibility to acidic conditions. , 2018, Biochemical and biophysical research communications.

[6]  Parissa Farnia,et al.  Drug-resistant Mycobacterium tuberculosis: Epidemiology and role of morphological alterations. , 2017, Journal of global antimicrobial resistance.

[7]  R. Mondal,et al.  PknG supports mycobacterial adaptation in acidic environment , 2018, Molecular and Cellular Biochemistry.

[8]  T. Clark,et al.  Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis , 2018, Nature Genetics.

[9]  R. Landmann,et al.  Survival of Mycobacterium tuberculosis and Mycobacterium bovis BCG in lysosomes in vivo. , 2017, Microbes and infection.

[10]  Jianping Xie,et al.  Mycobacterium tuberculosis Rv1265 promotes mycobacterial intracellular survival and alters cytokine profile of the infected macrophage , 2016, Journal of biomolecular structure & dynamics.

[11]  J. Reddy,et al.  PE11, a PE/PPE family protein of Mycobacterium tuberculosis is involved in cell wall remodeling and virulence , 2016, Scientific Reports.

[12]  Jianping Xie,et al.  Rv3369 Induces Cytokine Interleukin-1β Production and Enhances Mycobacterium smegmatis Intracellular Survival. , 2016, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[13]  M. Cox,et al.  P1 Ref Endonuclease: A Molecular Mechanism for Phage-Enhanced Antibiotic Lethality , 2016, PLoS genetics.

[14]  C. Liu,et al.  Mycobacterium tuberculosis Mce3E Suppresses Host Innate Immune Responses by Targeting ERK1/2 Signaling , 2015, The Journal of Immunology.

[15]  G. Gao,et al.  Mycobacterium tuberculosis suppresses innate immunity by coopting the host ubiquitin system , 2015, Nature Immunology.

[16]  Hang Yang,et al.  Isolation and complete genome sequence of a novel virulent mycobacteriophage, CASbig , 2015, Virologica Sinica.

[17]  J. Dennis,et al.  Burkholderia cepacia Complex Phage-Antibiotic Synergy (PAS): Antibiotics Stimulate Lytic Phage Activity , 2014, Applied and Environmental Microbiology.

[18]  M. Drancourt,et al.  Mycobacteriophage-drived diversification of Mycobacterium abscessus , 2014, Biology Direct.

[19]  G. Hatfull,et al.  Mutational Analysis of the Mycobacteriophage BPs Promoter PR Reveals Context-Dependent Sequences for Mycobacterial Gene Expression , 2014, Journal of bacteriology.

[20]  Jianping Xie,et al.  Mycobacterium tuberculosis Rv3402c Enhances Mycobacterial Survival within Macrophages and Modulates the Host Pro-Inflammatory Cytokines Production via NF-Kappa B/ERK/p38 Signaling , 2014, PloS one.

[21]  Han Liu,et al.  A mycobacteriophage‐derived trehalose‐6,6'‐dimycolate‐binding peptide containing both antimycobacterial and anti‐inflammatory abilities , 2013, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[22]  R. Coppel,et al.  Identification of a Novel Gene Product That Promotes Survival of Mycobacterium smegmatis in Macrophages , 2012, PloS one.

[23]  D. Schnappinger,et al.  Acid-Susceptible Mutants of Mycobacterium tuberculosis Share Hypersusceptibility to Cell Wall and Oxidative Stress and to the Host Environment , 2008, Journal of bacteriology.

[24]  Sahadevan Raman,et al.  Nitrile-inducible gene expression in mycobacteria. , 2009, Tuberculosis.

[25]  H. Kress,et al.  Dynamic life and death interactions between Mycobacterium smegmatis and J774 macrophages , 2006, Cellular microbiology.

[26]  V. Fischetti,et al.  PlyPH, a Bacteriolytic Enzyme with a Broad pH Range of Activity and Lytic Action against Bacillus anthracis , 2006, Journal of bacteriology.

[27]  Jun Liu,et al.  AsnB Is Involved in Natural Resistance of Mycobacterium smegmatis to Multiple Drugs , 2006, Antimicrobial Agents and Chemotherapy.

[28]  J. Pelletier,et al.  Antimicrobial drug discovery through bacteriophage genomics , 2004, Nature Biotechnology.

[29]  E. M. Fozo,et al.  Shifts in the Membrane Fatty Acid Profile of Streptococcus mutans Enhance Survival in Acidic Environments , 2004, Applied and Environmental Microbiology.

[30]  D. Sherman,et al.  The secret lives of the pathogenic mycobacteria. , 2003, Annual review of microbiology.

[31]  P. Brennan Structure, function, and biogenesis of the cell wall of Mycobacterium tuberculosis. , 2003, Tuberculosis.

[32]  Vincent A. Fischetti,et al.  Rapid Killing of Streptococcus pneumoniae with a Bacteriophage Cell Wall Hydrolase , 2001, Science.

[33]  M. Rohde,et al.  Characterization of the intracellular survival of Mycobacterium avium ssp. paratuberculosis: phagosomal pH and fusogenicity in J774 macrophages compared with other mycobacteria , 2001, Cellular microbiology.

[34]  P D Nichols,et al.  Evaluation of extraction methods for recovery of fatty acids from lipid-producing microheterotrophs. , 2000, Journal of microbiological methods.

[35]  H. Nikaido,et al.  A mutant of Mycobacterium smegmatis defective in the biosynthesis of mycolic acids accumulates meromycolates. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Ames,et al.  A bacteriolytic agent that detects and kills Bacillus anthracis , 2022 .