Bacteria and fungi continue to develop new ways to adapt and survive the lethal or biostatic effects of antimicrobials through myriad mechanisms. Novel antibiotic resistance genes such as lsa(C), erm(44), VCC-1, mcr-1, mcr-2, mcr-3, mcr-4, bla and bla were discovered through comparative genomics and further functional studies. As well, mutations in genes that hitherto were unknown to confer resistance to antimicrobials, such as trm, PP2C, rpsJ, HSC82, FKS2 and Rv2887, were shown by genomics and transcomplementation assays to mediate antimicrobial resistance in Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecium, Saccharomyces cerevisae, Candida glabrata and Mycobacterium tuberculosis, respectively. Thus, genomics, transcriptomics and metagenomics, coupled with functional studies are the future of antimicrobial resistance research and novel drug discovery or design.
Summary Our inability to cultivate most microorganisms, specifically bacteria, in the laboratory has for many years restricted our view and understanding of the bacterial meta‐resistome in all living and nonliving environments. As a result, reservoirs, sources and distribution of antibiotic resistance genes (ARGS) and antibiotic‐producers, as well as the effects of human activity and antibiotics on the selection and dissemination of ARGs were not well comprehended. With the advances made in the fields of metagenomics and metatranscriptomics, many of the hitherto little‐understood concepts are becoming clearer. Further, the discovery of antibiotics such as lugdinin and lactocillin from the human microbiota, buttressed the importance of these new fields. Metagenomics and metatranscriptomics are becoming important clinical diagnostic tools for screening and detecting pathogens and ARGs, assessing the effects of antibiotics, other xenobiotics and human activity on the environment, characterizing the microbiome and the environmental resistome with lesser turnaround time and decreasing cost, as well as discovering antibiotic‐producers. However, challenges with accurate binning, skewed ARGs databases, detection of less abundant and allelic variants of ARGs and efficient mobilome characterization remain. Ongoing efforts in long‐read, phased‐ and single‐cell sequencing, strain‐resolved binning, chromosomal‐conformation capture, DNA‐methylation binning and deep‐learning bioinformatic approaches offer promising prospects in reconstructing complete strain‐level genomes and mobilomes from metagenomes.
Zoonoses present a major public health threat and are estimated to account for a substantial part of the infectious disease burden in low-income countries. The severity of zoonotic diseases is compounded by factors such as poverty, living in close contact with livestock and wildlife, immunosuppression as well as coinfection with other diseases. The interconnections between humans, animals and the environment are essential to understand the spread and subsequent containment of zoonoses. We searched three scientific databases for articles relevant to the epidemiology of bacterial zoonoses/zoonotic bacterial pathogens, including disease prevalence and control measures in humans and multiple animal species, in various African countries within the period from 2008 to 2018. The review identified 1966 articles, of which 58 studies in 29 countries met the quality criteria for data extraction. The prevalence of brucellosis, leptospirosis, Q fever ranged from 0–40%, 1.1–24% and 0.9–28.2%, respectively, depending on geographical location and even higher in suspected outbreak cases. Risk factors for human zoonotic infection included exposure to livestock and animal slaughters. Dietary factors linked with seropositivity were found to include consumption of raw milk and locally fermented milk products. It was found that zoonoses such as leptospirosis, brucellosis, Q fever and rickettsiosis among others are frequently under/misdiagnosed in febrile patients seeking treatment at healthcare centres, leading to overdiagnoses of more familiar febrile conditions such as malaria and typhoid fever. The interactions at the human–animal interface contribute substantially to zoonotic infections. Seroprevalence of the various zoonoses varies by geographic location and species. There is a need to build laboratory capacity and effective surveillance processes for timely and effective detection and control of zoonoses in Africa. A multifaceted ‘One Health’ approach to tackle zoonoses is critical in the fight against zoonotic diseases. The impacts of zoonoses include: (1) Humans are always in contact with animals including livestock and zoonoses are causing serious life-threatening infections in humans. Almost 75% of the recent major global disease outbreaks have a zoonotic origin. (2) Zoonoses are a global health challenge represented either by well-known or newly emerging zoonotic diseases. (3) Zoonoses are caused by all-known cellular (bacteria, fungi and parasites) and noncellular (viruses or prions) pathogens. (4) There are limited data on zoonotic diseases from Africa. The fact that human health and animal health are inextricably linked, global coordinated and well-established interdisciplinary research efforts are essential to successfully fight and reduce the health burden due to zoonoses. This critically requires integrated data from both humans and animals on zoonotic diseases.
Coagulase-negative staphylococci (CoNS) have engendered substantial interest in recent years as pathogenic causes of infections in both human and veterinary medicine, especially in the immunocompromised, critically ill, long-term hospitalized and in those harboring invasive medical devices such as catheters. They have been implicated in infections such as urinary tract infections, bloodstream infections, and invasive device-related infections, and are responsible for substantial economic losses in livestock production. The advancement of diagnostic techniques has increased our understanding of their molecular mechanisms of pathogenicity, even though distinguishing between innocuousness and pathogenicity is still challenging. The incidence of CoNS varied across the continent in humans and animals (mainly cattle), ranging from 6% to 68% in suspected human infections and from 3% to 61.7% in suspected animal infections, distributed across different geographic locations. Furthermore, there were varying antibiotic resistance patterns observed in CoNS isolates, with high methicillin resistance in some cases, leading to crossresistance against many antibiotics. Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus xylosus were most commonly reported in studies herein reviewed, while the enterotoxin C gene, atl E gene, ica gene, and hemolysin virulence factors were linked with enhanced pathogenicity. Advancement in identification and typing methods, including whole genome sequencing, virulence screening, and the assessment of the immune status of subjects in studies will help to thoroughly assess the true pathogenic potential of isolated CoNS species in developing countries. Careful antibiotic stewardship guidelines should be followed due to the ability of CoNS to develop multidrug resistance.
Coagulase-negative staphylococci (CoNS) are increasingly associated with nosocomial infections, especially among the immunocompromised and those with invasive medical devices, posing a significant concern. We report on clinical multidrug-resistant CoNS from the uMgungundlovu District, KwaZulu-Natal Province, South Africa, as emerging pathogens. One hundred and thirty presumptive CoNS were obtained from blood cultures. Culture, biochemical tests, and the Staphaurex™ Latex Agglutination Test were used for the initial identification of CoNS isolates; confirmation and speciation were undertaken by the VITEK 2 system. Susceptibilities of isolates against a panel of 20 antibiotics were determined using the Kirby-Bauer disk diffusion method, and the multiple antibiotic resistance (MAR) indices of the isolates were determined. The polymerase chain reaction (PCR) was used to amplify the mecA gene to confirm methicillin resistance. Overall, 89/130 presumptive CoNS isolates were confirmed as CoNS by the VITEK 2 system. Of these, 68 (76.4%) isolates were putatively methicillin-resistant by the phenotypic cefoxitin screen test and 63 (92.6%) were mecA positive. Staphylococcus epidermidis (19.1%), S. hominis ssp hominis (15.7%), and S. haemolyticus (16.9%) were the most common CoNS species. Isolates showed high percentage resistance against penicillin (100.0%), erythromycin (74.2%), and azithromycin (74.2%) while displaying high susceptibilities to linezolid (95.5%), gentamicin (95.5%), and tigecycline (94.4%). Multidrug resistance (MDR) was observed in 76.4% of isolates. MAR index calculation revealed 71.9% of isolates with MAR index >0.2 and 20.2% >0.5. Isolates with the highest MAR indices (0.7 and 0.8) were recovered from the neonatal intensive care unit. Fifty-one MDR antibiograms were observed. The high prevalence of methicillin resistance and multidrug resistance in several species of CoNS necessitates surveillance of this emerging pathogen, currently considered a contaminant of microbial cultures.
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