Genomic and Resistance Epidemiology of Gram-Negative Bacteria in Africa: a Systematic Review and Phylogenomic Analyses from a One Health Perspective

Abstract

Antibiotic resistance (AR) remains a major threat to public and animal health globally. However, AR ramifications in developing countries are worsened by limited molecular diagnostics, expensive therapeutics, inadequate numbers of skilled clinicians and scientists, and unsanitary environments. The epidemiology of Gram-negative bacteria, their AR genes, and geographical distribution in Africa are described here. Data were extracted and analyzed from English-language articles published between 2015 and December 2019. The genomes and AR genes of the various species, obtained from the Pathosystems Resource Integration Center (PATRIC) and NCBI were analyzed phylogenetically using Randomized Axelerated Maximum Likelihood (RAxML) and annotated with Figtree. The geographic location of resistant clones/clades was mapped manually. Thirty species from 31 countries and 24 genera from 41 countries were analyzed from 146 articles and 3,028 genomes, respectively. Genes mediating resistance to β-lactams (including blaTEM-1, blaCTX-M, blaNDM, blaIMP, blaVIM, and blaOXA-48/181), fluoroquinolones (oqxAB, qnrA/B/D/S, gyrA/B, and parCE mutations, etc.), aminoglycosides (including armA and rmtC/F), sulfonamides (sul1/2/3), trimethoprim (dfrA), tetracycline [tet(A/B/C/D/G/O/M/39)], colistin (mcr-1), phenicols (catA/B, cmlA), and fosfomycin (fosA) were mostly found in Enterobacter spp. and Klebsiella pneumoniae, and also in Serratia marcescens, Escherichia coli, Salmonella enterica, Pseudomonas, Acinetobacter baumannii, etc., on mostly IncF-type, IncX3/4, ColRNAI, and IncR plasmids, within IntI1 gene cassettes, insertion sequences, and transposons. Clonal and multiclonal outbreaks and dissemination of resistance genes across species and countries and between humans, animals, plants, and the environment were observed; Escherichia coli ST103, K. pneumoniae ST101, S. enterica ST1/2, and Vibrio cholerae ST69/515 were common strains. Most pathogens were of human origin, and zoonotic transmissions were relatively limited. IMPORTANCE Antibiotic resistance (AR) is one of the major public health threats and challenges to effective containment and treatment of infectious bacterial diseases worldwide. Here, we used different methods to map out the geographical hot spots, sources, and evolutionary epidemiology of AR. Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., Neisseria meningitis/gonorrhoeae, Vibrio cholerae, Campylobacter jejuni, etc., were common pathogens shuttling AR genes in Africa. Transmission of the same clones/strains across countries and between animals, humans, plants, and the environment was observed. We recommend Enterobacter spp. or K. pneumoniae as better sentinel species for AR surveillance.

Acinetobacter baumannii Antibiotic Resistance Mechanisms

“…As mentioned above in text, efflux pumps AdeIJK and LmrS confer resistance to trimethoprim [ 148 ]. Another pump, the RND plasmid-borne OqxAB, links with resistance to trimethoprim, quinolones, tetracyclines, glycylcycline, and nitrofurans [ 188 , 189 ].…”

Emerging Transcriptional and Genomic Mechanisms Mediating Carbapenem and Polymyxin Resistance in Enterobacteriaceae : a Systematic Review of Current Reports

“…These enzymes are frequently plasmid-borne genes, allowing for the dissemination of genes within and between Gram-negative bacteria species. This results in resistance toward penicillin, cephalosporins, carbapenems, and/or monobactams ( 29 , 202 , 203 ). Carbapenem resistance in Enterobacteriaceae is mediated mainly by the production of carbapenemases ( 11 ).…”

Molecular Epidemiology, Risk Factors and Clinical Outcomes of Carbapenem- and Polymyxin-Resistant Gram-negative Bacterial Infections in Pregnant Women and Infants: A Systematic Review

“…and Pseudomonas sp ., although reports on outbreaks were either associated with carbapenem resistance 34,36 or absent. Hence, outbreaks involving CR-GNB that were also polymyxin resistant could also be referred to as PR-GNB outbreaks, which makes such infections very difficult to manage 1,2,4,9 . The largest collection of PR-GNB was recorded in Malaysia from preterm infants in a NICU in 2016, eight of which were carbapenem-resistant K. pneumoniae 34 .…”

“…The immediate genetic environment of the NDM-5 on these plasmids were exactly the same or similar, suggesting that same plasmids and/or clones were mediating the spread of NDM-5 within and between species 31,45 . The higher mobility of these carbapenemases may explain their faster dissemination between neonates in wards and hospitals during outbreaks and evinces the need to undertake molecular analyses of isolates to comprehend their epidemiology 1,2,4,9,69 .…”

“…Resistance to antimicrobials remain a major challenge to public health, veterinary medicine, agriculture and aquaculture globally, owing to the limited or no therapeutic option available to treat multidrug-resistant (MDR) infections [1][2][3][4][5] . To avoid depleting our antibiotics arsenals against infectious pathogens, certain agents are reserved as last-line drugs to fight difficult-totreat infections [6][7][8] .…”