RNA polymerase mutations cause cephalosporin resistance in clinical Neisseria gonorrhoeae isolates

eLife

Yi Wang¹  Suzanne Walker²  Samantha G Palace³  Michael A Welsh³  Kevin Cole³  Daniel HF Rubin³  Tatum D Mortimer⁴  Yonatan H Grad⁴  David W Eyre⁵ 

[1] Center for Communicable Disease Dynamics, Harvard T. H. Chan School of Public Health, Boston, United States;Big Data Institute, University of Oxford, Oxford, United Kingdom;Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, United States;Department of Microbiology, Harvard Medical School, Boston, United States;Public Health England, Royal Sussex County Hospital, Brighton, United Kingdom;

关键词: Neisseria gonorrhoeae;    antimicrobial resistance;    gonorrhea;    cephalosporins;    antibiotic resistance;   

DOI  :  10.7554/eLife.51407

来源: DOAJ

【 摘 要 】

Increasing Neisseria gonorrhoeae resistance to ceftriaxone, the last antibiotic recommended for empiric gonorrhea treatment, poses an urgent public health threat. However, the genetic basis of reduced susceptibility to ceftriaxone is not completely understood: while most ceftriaxone resistance in clinical isolates is caused by target site mutations in penA, some isolates lack these mutations. We show that penA-independent ceftriaxone resistance has evolved multiple times through distinct mutations in rpoB and rpoD. We identify five mutations in these genes that each increase resistance to ceftriaxone, including one mutation that arose independently in two lineages, and show that clinical isolates from multiple lineages are a single nucleotide change from ceftriaxone resistance. These RNA polymerase mutations cause large-scale transcriptional changes without altering susceptibility to other antibiotics, reducing growth rate, or deranging cell morphology. These results underscore the unexpected diversity of pathways to resistance and the importance of continued surveillance for novel resistance mutations.

【 授权许可】

Unknown