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Genetics and regulation of outer membrane protein expression by quinolone resistance loci nfxB, nfxC, and cfxB
D C Hooper1, J S Wolfson, M A Bozza
1Infectious Disease Unit, Medical Services, Massachusetts General Hospital, Harvard Medical School, Boston 02114-2696.
Abstract:
Quinolone resistance mutations (cfxB1, marA1, and soxQ1) that reduce porin outer membrane protein OmpF map near 34 min on the Escherichia coli chromosome. Another such mutation, nfxC1, was found in strain KF131 (nfxB, 19 min). nfxC1 and cfxB1 mutants (selected with quinolones) differed slightly but reproducibly from marA1 (selected with tetracycline) and soxQ1 (selected with menadione) mutants in quinolone resistance and linkage to zdd2208::Tn10kan (33.7 min). For nfxB nfxC1 and cfxB1 mutants, as previously shown for marA mutants, resistance and reduced OmpF required the micF locus encoding an antisense RNA complementary to ompF mRNA and were associated with increased micF expression.
Insights
New quinolone resistance mutations in Escherichia coli reduce the OmpF porin. These mutations, affecting gene expression, require the micF locus for resistance and reduced OmpF levels.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Quinolone antibiotics are crucial for treating bacterial infections.
- Resistance to quinolones can arise from mutations affecting bacterial outer membrane proteins, such as OmpF.
- Understanding the genetic basis of quinolone resistance is vital for developing effective treatments.
Purpose of the Study:
- To identify and characterize new mutations conferring quinolone resistance in Escherichia coli.
- To investigate the role of the OmpF porin and the micF locus in quinolone resistance mechanisms.
Main Methods:
- Mutagenesis and selection of quinolone-resistant Escherichia coli strains.
- Genetic mapping of resistance mutations on the E. coli chromosome.
- Analysis of OmpF porin expression and micF gene expression.
Main Results:
- Identified quinolone resistance mutations (cfxB1, marA1, soxQ1, nfxC1) located at different chromosomal positions.
- Demonstrated that these mutations reduce the expression of the OmpF porin.
- Showed that resistance and reduced OmpF levels require the micF locus and are associated with increased micF expression.
Conclusions:
- Multiple genetic loci contribute to quinolone resistance in E. coli by affecting OmpF porin expression.
- The micF locus plays a critical role in mediating quinolone resistance through an antisense RNA mechanism.
- These findings provide insights into the complex mechanisms of antibiotic resistance in bacteria.