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A Bacteriophage Capsid Protein Is an Inhibitor of a Conserved Transcription Terminator of Various Bacterial Pathogens

Ghosh, Gairika ; Reddy, Jayavardhana ; Sambhare, Susmit ; Sen, Ranjan Henkin, Tina M.

Journal of bacteriology, 2018-01, Vol.200 (1) [Periódico revisado por pares]

United States: American Society for Microbiology

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Título:
A Bacteriophage Capsid Protein Is an Inhibitor of a Conserved Transcription Terminator of Various Bacterial Pathogens
Autor: Ghosh, Gairika ; Reddy, Jayavardhana ; Sambhare, Susmit ; Sen, Ranjan
Henkin, Tina M.
Assuntos: Adenosine triphosphatase ; Adenosine Triphosphatases - antagonists & inhibitors ; Antibiotics ; Antiinfectives and antibacterials ; Antimicrobial agents ; Bacteria ; Bacteriology ; Bacteriophages - chemistry ; Binding ; Blocking ; Capsid protein ; Capsid Proteins - genetics ; Capsid Proteins - metabolism ; Capsid Proteins - pharmacology ; Corynebacterium glutamicum ; DNA-Directed RNA Polymerases - metabolism ; E coli ; Elongation ; Escherichia coli - genetics ; Escherichia coli - pathogenicity ; Gene expression ; Gram-Negative Bacteria - drug effects ; Gram-Negative Bacteria - genetics ; Gram-Negative Bacteria - pathogenicity ; Gram-positive bacteria ; Gram-Positive Bacteria - drug effects ; Gram-Positive Bacteria - genetics ; Gram-Positive Bacteria - pathogenicity ; Homology ; Inhibitors ; Mycobacterium - drug effects ; Mycobacterium tuberculosis - drug effects ; Mycobacterium tuberculosis - genetics ; Mycobacterium tuberculosis - pathogenicity ; Nature conservation ; Nucleotide sequence ; Pathogens ; Peptides ; Phylogeny ; Protein Binding ; Proteins ; Recombinant Proteins - metabolism ; Rho Factor - antagonists & inhibitors ; Rho Factor - genetics ; Rho Factor - metabolism ; Ribonucleic acid ; RNA ; Salmonella ; Sequence Homology, Nucleic Acid ; Substrates ; Transcription elongation ; Transcription Termination, Genetic - drug effects ; Translocase ; Tuberculosis ; Vibrio cholerae - drug effects ; Vibrio cholerae - genetics ; Vibrio cholerae - pathogenicity ; Waterborne diseases ; Xanthomonas - drug effects ; Xanthomonas campestris
É parte de: Journal of bacteriology, 2018-01, Vol.200 (1)
Notas: Citation Ghosh G, Reddy J, Sambhare S, Sen R. 2018. A bacteriophage capsid protein is an inhibitor of a conserved transcription terminator of various bacterial pathogens. J Bacteriol 200:e00380-17. https://doi.org/10.1128/JB.00380-17.
Descrição: Rho is a hexameric molecular motor that functions as a conserved transcription terminator in the majority of bacterial species and is a potential drug target. Psu is a bacteriophage P4 capsid protein that inhibits Rho by obstructing its ATPase and translocase activities. In this study, we explored the anti-Rho activity of Psu for Rho proteins from different pathogens. Sequence alignment and homology modeling of Rho proteins from pathogenic bacteria revealed the conserved nature of the Psu-interacting regions in all these proteins. We chose Rho proteins from various pathogens, including , , , , , , , , and The purified recombinant Rho proteins of these organisms showed variable rates of ATP hydrolysis on poly(rC) as the substrate and were capable of releasing RNA from the transcription elongation complexes. Psu was capable of inhibiting these two functions of all these Rho proteins. pulldown assays revealed direct binding of Psu with many of these Rho proteins. expression of induced killing of , , , and expressing Rho indicating Psu-induced inhibition of Rho proteins of these strains under physiological conditions. We propose that the "universal" inhibitory function of the Psu protein against the Rho proteins from both Gram-negative and Gram-positive bacteria could be useful for designing peptides with antimicrobial functions and that these peptides could contribute to synergistic antibiotic treatment of the pathogens by compromising the Rho functions. Bacteriophage-derived protein factors modulating different bacterial processes could be converted into unique antimicrobial agents. Bacteriophage P4 capsid protein Psu is an inhibitor of the transcription terminator Rho. Here we show that apart from antagonizing Rho, Psu is able to inhibit Rho proteins from various phylogenetically unrelated Gram-negative and Gram-positive pathogens. Upon binding to these Rho proteins, Psu inhibited them by affecting their ATPase and RNA release functions. The expression of Psu kills various pathogens, such as and species. Hence, Psu could be useful for identifying peptide sequences with anti-Rho activities and might constitute part of synergistic antibiotic treatment against pathogens.
Editor: United States: American Society for Microbiology
Idioma: Inglês

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A Bacteriophage Capsid Protein Is an Inhibitor of a Conserved Transcription Terminator of Various Bacterial Pathogens

Ghosh, Gairika ; Reddy, Jayavardhana ; Sambhare, Susmit ; Sen, Ranjan Henkin, Tina M.

United States: American Society for Microbiology

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