A novel gene amplification causes upregulation of the PatAB ABC transporter and fluoroquinolone resistance in Streptococcus pneumoniae

Antimicrobial Agents and Chemotherapy
Alison J BaylayLaura J V Piddock

Abstract

Overexpression of the ABC transporter genes patA and patB confers efflux-mediated fluoroquinolone resistance in Streptococcus pneumoniae and is also linked to pneumococcal stress responses. Although upregulation of patAB has been observed in many laboratory mutants and clinical isolates, the regulatory mechanisms controlling expression of these genes are unknown. In this study, we aimed to identify the cause of high-level constitutive overexpression of patAB in M184, a multidrug-resistant mutant of S. pneumoniae R6. Using a whole-genome transformation and sequencing approach, we identified a novel duplication of a 9.2-kb region of the M184 genome which included the patAB genes. This duplication did not affect growth and was semistable with a low segregation rate. The expression levels of patAB in M184 were much higher than those that could be fully explained by doubling of the gene dosage alone, and inactivation of the first copy of patA had no effect on multidrug resistance. Using a green fluorescent protein reporter system, increased patAB expression was ascribed to transcriptional read-through from a tRNA gene upstream of the second copy of patAB. This is the first report of a large genomic duplication causing antibiotic res...Continue Reading

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Jul 28, 2016·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Bryan D Schindler, Glenn W Kaatz
Jun 27, 2017·Journal of Medical Microbiology·Grace El MoujaberMonzer Hamze
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Jun 30, 2019·Research in Microbiology·Cédric OrelleJean-Michel Jault
Nov 20, 2020·Chemical Reviews·Philip A KlenoticEdward W Yu

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Datasets Mentioned

BETA
AE007317.1

Methods Mentioned

BETA
PCR
Illumina sequencing
reverse transcription-PCR
Fluorescence

Software Mentioned

SAMtools
Artemis
mpileup
Velvet
TransTermHP
BCFtools
Bowtie2
BLAST
STAMP
Promoter

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