Exploration of the Neisseria Resistome Reveals Resistance Mechanisms in Commensals That May Be Acquired by N. gonorrhoeae through Horizontal Gene Transfer.

Michael A Fiore,Crista B Wadsworth,André O Hudson,Narayan H Wong,Jordan C Raisman

doi:10.3390/antibiotics9100656

Michael A Fiore, Crista B Wadsworth + Show 3 more

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https://doi.org/10.3390/antibiotics9100656

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Journal: Antibiotics	Publication Date: Sep 30, 2020
Citations: 35	License type: CC BY 4.0

Affiliation: Rochester Institute of Technology

Abstract

Nonpathogenic Neisseria transfer mutations encoding antibiotic resistance to their pathogenic relative Neisseria gonorrhoeae. However, the resistance genotypes and subsequent phenotypes of nonpathogens within the genus have been described infrequently. Here, we characterize the minimum inhibitory concentrations (MICs) of a panel of Neisseria (n = 26)—including several commensal species—to a suite of diverse antibiotics. We furthermore use whole genome sequencing and the Comprehensive Antibiotic Resistance Database Resistance Gene Identifier (RGI) platform to predict putative resistance-encoding mutations. Resistant isolates to all tested antimicrobials including penicillin (n = 5/26), ceftriaxone (n = 2/26), cefixime (n = 3/26), tetracycline (n = 10/26), azithromycin (n = 11/26), and ciprofloxacin (n = 4/26) were found. In total, 63 distinct mutations were predicted by RGI to be involved in resistance. The presence of several mutations had clear associations with increased MIC such as DNA gyrase subunit A (gyrA) (S91F) and ciprofloxacin, tetracycline resistance protein (tetM) and 30S ribosomal protein S10 (rpsJ) (V57M) and tetracycline, and TEM-type β-lactamases and penicillin. However, mutations with strong associations to macrolide and cephalosporin resistance were not conclusive. This work serves as an initial exploration into the resistance-encoding mutations harbored by nonpathogenic Neisseria, which will ultimately aid in prospective surveillance for novel resistance mechanisms that may be rapidly acquired by N. gonorrhoeae.

Highlights

The emergence of antibiotic resistance in pathogenic bacteria presents a challenge for successful treatment of infections and is a global threat to public health
N. gonorrhoeae Antibiotic Resistance (AR) Bank # 0936 was resistant to tetracycline and ciprofloxacin and was just below the reduced susceptibility threshold for azithromycin
With the breakpoint at 2 μg/mL); N. gonorrhoeae AR Bank # 0937 was resistant to penicillin and ciprofloxacin and was just below the reduced susceptibility threshold for tetracycline (1.5 μg/mL with the breakpoint at 2 μg/mL); and N. gonorrhoeae AR Bank # 0938 was resistant to penicillin, tetracycline, and ciprofloxacin

Summary

Introduction

The emergence of antibiotic resistance in pathogenic bacteria presents a challenge for successful treatment of infections and is a global threat to public health. While resistance can arise in bacteria via de novo mutations, it can be horizontally transferred from environmental [2,3,4], animal [5,6,7], or human-associated [8,9,10] microbial communities. There are a number of mechanisms that are employed by bacteria to circumvent the efficacy of antibiotics. These include but are not limited to decreased drug influx, target modification, antibiotic degradation, and increased efflux through pumps [11]. The threat of rapid resistance acquisition via horizontal gene transfer (HGT) of all these mechanisms is exponentially amplified in bacteria that are naturally competent and highly recombinogenic such as the Neisseria. Antimicrobial resistance is an increasing problem within N. gonorrhoeae, with over half of all 550,000 reported infections in the U.S in 2017 resistant to at least one antibiotic [1]

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