The emergence and persistence of antimicrobial resistance is driven by varied factors including the indiscriminate use of antibiotics and variable drug efficacy and presents a major threat to the control of infectious diseases. Despite the high burden of disease in sub-Saharan Africa and the potential health and economic consequences, the level of research on antimicrobial resistance in the region remains unknown. Little data exists to quantify the contribution of different factors to the current levels of antimicrobial resistance. To identify the factors that contribute most to the emergence, amplification, persistence and dissemination of antimicrobial resistance in humans and animals, we used the PRISMA 2009 guidelines to conduct a systematic review of studies on antibiotic-resistant enteric bacteria in Eastern Africa. We searched PubMed and Google Scholar databases and identified 2,155 probable articles, of which 89 studies on humans and 28 on animals remained after full-text review. These were articles from Kenya, Tanzania, Uganda, Ethiopia, Rwanda and Burundi, published between 1974 and 2013, that reported resistance in Salmonella, Shigella, Escherichia coli and Vibrio sp. The majority (98%) of human studies were based on hospital- (rather than community-wide) sampling and although they report high levels of antimicrobial resistance in the region, study design and methodological differences preclude conclusions about the magnitude and trends of antimicrobial resistance. To remedy this, we discuss and propose minimum reporting guidelines for the level of detail that should be explicitly provided for antimicrobial resistance study designs, testing of samples and reporting of results that would permit comparative inferences and enable meta-analyses. Further, we advocate for increased focus on community- rather than hospital-based sampling to provide a better indication of population-wide trends in antimicrobial resistance. This approach, together with the establishment of a robust regional surveillance network, should over time build a pool of evidence-based data useful for policy decisions and interventions aimed at controlling antimicrobial resistance.

Large multidrug resistance plasmids of the A/C incompatibility complex (IncA/C) have been found in a diverse group of Gram-negative commensal and pathogenic bacteria. We present three completed sequences from IncA/C plasmids that originated from Escherichia coli (cattle) and Salmonella enterica serovar Newport (human) and that carry the cephamycinase gene bla _CMY-2 . These large plasmids (148 to 166 kbp) share extensive sequence identity and synteny. The most divergent plasmid, peH4H, has lost several conjugation-related genes and has gained a kanamycin resistance region. Two of the plasmids (pAM04528 and peH4H) harbor two copies of bla _CMY-2 , while the third plasmid (pAR060302) harbors a single copy of the gene. The majority of single-nucleotide polymorphisms comprise nonsynonymous mutations in floR . A comparative analysis of these plasmids with five other published IncA/C plasmids showed that the bla _CMY-2 plasmids from E. coli and S. enterica are genetically distinct from those originating from Yersinia pestis and Photobacterium damselae and distal to one originating from Yersinia ruckeri . While the overall similarity of these plasmids supports the likelihood of recent movements among E. coli and S. enterica hosts, their greater divergence from Y. pestis or Y. ruckeri suggests less recent plasmid transfer among these pathogen groups.

Vibrio parahaemolyticus is an emerging bacterial pathogen capable of causing inflammatory gastroenteritis, wound infections and septicemia. As a food-borne illness, infection is most frequently associated with the consumption of raw or undercooked seafood, particularly shellfish. It is the primary cause of Vibrio-associated food-borne illness in the United States and the leading cause of food-borne illness in Japan. The larger of its two chromosomes harbors a set of genes encoding type III section system 1 (T3SS1), a virulence factor present in all V. parahaemolyticus strains that is similar to the Yersinia ysc T3SS. T3SS1 translocates effector proteins into eukaryotic cells where they induce changes to cellular physiology and modulate host-pathogen interactions. T3SS1 is also responsible for cytotoxicity towards several different cultured cell lines as well as mortality in a mouse model. Herein we used RNA-seq to obtain global transcriptome patterns of V. parahaemolyticus under conditions that either induce (growth in DMEM media, in trans expression of transcriptional regulator exsA) or repress T3SS1 expression (growth in LB-S media, in trans exsD expression) and during infection of HeLa cells over time. Comparative transcriptomic analysis demonstrated notable differences in the expression patterns under inducing conditions and was also used to generate an expression profile of V. parahaemolyticus during infection of HeLa cells. In addition, we identified several new genes that are associated with T3SS1 expression and may warrant further study.

The prevalence of antimicrobial drug-resistant bacteria is typically highest in younger animals, and prevalence is not necessarily related to recent use of antimicrobial drugs. In dairy cattle, we hypothesize that antimicrobial drug-resistant, neonate-adapted bacteria are responsible for the observed high frequencies of resistant Escherichia coli in calves. To explore this issue, we examined the age distribution of antimicrobial drug-resistant E. coli from Holstein cattle at a local dairy and conducted an experiment to determine if low doses of oxytetracycline affected the prevalence of antimicrobial drug-resistant E. coli . Isolates resistant to tetracycline (>4 μg/ml) were more prevalent in 12 μg/ml), sulfadiazine (>512 μg/ml), and tetracycline (>4 μg/ml) (SSuT), and this resistance pattern was most prevalent during the period when calves were on milk diets. To determine if prevalence was a function of differential fitness, we orally inoculated animals with nalidixic acid-resistant strains of SSuT E. coli and susceptible E. coli . Shedding of SSuT E. coli was significantly greater than that of susceptible strains in neonatal calves ( P < 0.001), whereas there was no difference in older animals ( P = 0.5). These data support the hypothesis that active selection for traits linked to the SSuT phenotype are responsible for maintaining drug-resistant E. coli in this population of dairy calves.