Point mutation in the stop codon of MAV_RS14660 increases the growth rate of Mycobacterium avium subspecies hominissuis

Tomomi Kawakita, Tetsu Mukai, Mitsunori Yoshida, Hiroyuki Yamada, Masaaki Nakayama, Yuji Miyamoto, Masato Suzuki, Noboru Nakata, Takemasa Takii, Akihide Ryo, Naoya Ohara, Manabu Ato

Research output: Contribution to journalArticlepeer-review

Abstract

Mycobacterium avium subspecies hominissuis (MAH) is a pathogen that causes various non-tuberculous mycobacterial diseases in humans and animals worldwide. Among the genus, MAH is characterized by relatively slow growth. Here, we isolated a rapidly growing variant of the MAH 104 strain. The variant strain (named N104) exhibited an enhanced growth rate and higher motility compared to the parent MAH 104 strain (P104). Whole-genome sequencing analysis of N104 revealed the loss of the stop codon of MAV_RS14660 due to a single nucleotide replacement, resulting in the substitution of the codon for tryptophan. Notably, exclusion of the stop codon ligated the open reading frames and caused the fusion of two adjacent proteins. A revertant parent strain, in which a mutation was introduced to restore the stop codon, revealed that elimination of the stop codon in MAV_RS14660 was responsible for the N104 phenotype. Furthermore, we analysed the phenotypes of the parent and mutated strains by determining the functions of the MAV_RS14660 and MAV_RS14655 coding regions flanking the stop codon. The mutant strains, expected to express a fusion protein, exhibited increased resistance to antimicrobial drugs and exogenous copper toxicity compared to that of the parent strains. These findings suggest that the fusion of the MAV_RS14660- and MAV_RS14655-encoding regions in the mutant N104 strain could be related to the modified functions of these intrinsic proteins.

Original languageEnglish
JournalMicrobiology (Reading, England)
Volume167
Issue number2
DOIs
Publication statusPublished - Feb 1 2021

Keywords

  • growth rate
  • Mycobacterium avium subspecies hominissuis
  • single nucleotide replacement
  • sliding motility

ASJC Scopus subject areas

  • Microbiology

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