Antibiotic resistome of Salmonella typhi: molecular determinants for the emergence of drug resistance / 医学前沿

Resistome is a cluster of microbial genes encoding proteins with necessary functions to resist the action of antibiotics. Resistome governs essential and separate biological functions to develop resistance against antibiotics. The widespread clinical and nonclinical uses of antibiotics over the years have combined to select antibiotic-resistant determinants and develop resistome in bacteria. At present, the emergence of drug resistance because of resistome is a significant problem faced by clinicians for the treatment of Salmonella infection. Antibiotic resistome is a dynamic and ever-expanding component in Salmonella. The foundation of resistome in Salmonella is laid long before; therefore, the antibiotic resistome of Salmonella is reviewed, discussed, and summarized. We have searched the literature using PubMed, MEDLINE, and Google Scholar with related key terms (resistome, Salmonella, antibiotics, drug resistance) and prepared this review. In this review, we summarize the status of resistance against antibiotics in S. typhi, highlight the seminal work in the resistome of S. typhi and the genes involved in the antibiotic resistance, and discuss the various methods to identify S. typhi resistome for the proactive identification of this infection and quick diagnosis of the disease.

Resistome in gram-negative bacteria from soft cheese in Brazil / Resistoma em bactérias gram-negativas de queijo minas frescal no Brazil

Objective: evaluation of antibiotic resistance in Gram-negative microbiota from ready-to-eat cheese samples. Methodology: this research applied an adapted methodology to select from a food sample viable Gram-negative microbiota displaying antibiotic resistance. The selected food was a cheese that is commonly consumed without thermal processing, the Minas Frescal cheese. The evaluation was followed by a PCR screening in this resistant microbiota, for genes that provide resistance to antibiotics and also to the quaternary ammonium. Results: all cheese samples harbored a resistant microbiota. In 13.3% of the cheese samples analyzed, the resistance reached all ten different antibiotics tested and, in 80%, 8 to 10 different antibiotics. In antibiotics considered critics as the carbapenems: ertapenem presented resistant microbiota in 86.7% of the samples. In cephalosporins, the resistance reached 100% in the third generation (ceftazidime) and almost half of the samples (46.7%) in the fourth generation (cefepime). In genotypic research, seven different resistance genes were found in 69.2% of the bacterial pools, including the beta-lactamase-producing genes ctx, tem, shv, tetracycline-resistant genes, and a high rate of integrons class 1 and 2. Conclusion: the results indicate phenotypically and genotypically that the Minas Frescal cheese can harbor potential resistant microbiota. Therefore, the methodology used is a viable possibility and with a broader answer about the food microbiota role in resistance. This research corroborates the food area as an important sector to be managed to reduce the process of antibiotic resistance.

Objetivo: avaliação da resistência a antibióticos em microbiota Gram-negativa de amostras de queijo prontas para consumo. Metodologia: esta pesquisa aplicou uma metodologia adaptada para selecionar a microbiota Gram-negativa viável apresentando resistência a antibióticos em uma amostra de alimento. O alimento selecionado foi um queijo frequentemente consumido sem processamento térmico, o queijo Minas Frescal. A avaliação foi seguida de uma triagem por PCR, nesta microbiota resistente, para genes que fornecem resistência aos antibióticos e também ao quaternário de amônio. Resultados: todas as amostras de queijo apresentaram microbiota resistente. Em 13,3% dos queijos analisados essa resistência alcançou todos os 10 diferentes antibióticos testados e em 80% entre 8 e 10 antibióticos diferentes. Em antibióticos considerados críticos como os carbapenêmicos: ertapenem apresentou microbiota resistente em 86,7% das amostras. Nas cefalosporinas, a resistência atingiu 100% na terceira geração (ceftazidima) e quase a metade das amostras (46,7%) na quarta geração (cefepime). Na pesquisa genotípica, sete diferentes genes de resistência foram encontrados em 69,2% dos pools bacterianos, incluindo o genes produtores de beta-lactamase, genes de resistência à tetraciclina, ctx, tem, shv e uma alta taxa de integron classe 1 e 2. Conclusão: os resultados indicam fenotipicamente e genotipicamente que o queijo Minas Frescal pode apresentar uma potencial microbiota resistente. Portanto, a metodologia utilizada é uma possibilidade viável e com uma resposta mais ampla sobre o papel da microbiota na resistência. Esta pesquisa corrobora a área de alimentos como um setor importante a ser gerenciado para redução no processo de resistência a antibióticos.

The human gut resistome: Current concepts & future prospects

The human gut is home to a myriad of organisms. While some are harmless commensals, others are transient, pathogenic flora. The gut microbiome is composed of diverse bacterial flora, and apart from playing a major role in protecting from various infectious and non-infectious diseases, it plays an important role in resistance to antimicrobials. The collection of genes or genetic material that confers antimicrobial resistance constitutes the gut resistome, and it may involve the pathogens or commensals of the intestinal tract. The diversity of this gut resistome is influenced by various environmental factors including the diet and antibiotic exposure. This review highlights the recent concepts pertaining to the human gut resistome, factors affecting it, how it impacts human health and diseases, methods to study the resistome and potential therapeutic approaches.

RNA-seq analysis reveals resistome genes and signalling pathway associated with vancomycin-intermediate Staphylococcus aureus

Context: Vancomycin-intermediate Staphylococcus aureus remains one of the most prevalent multidrug-resistant pathogens causing healthcare infections that are difficult to treat. Aims: This study uses a comprehensive computational analysis to systematically investigate various gene expression profiles of resistant and sensitive S. aureus strains on exposure to antibiotics. Settings and Design: The transcriptional changes leading to the development of multiple antibiotic resistance were examined by an integrative analysis of nine differential expression experiments under selected conditions of vancomycin-intermediate and -sensitive strains for four different antibiotics using publicly available RNA-Seq datasets. Materials and Methods: For each antibiotic, three experimental conditions for expression analysis were selected to identify those genes that are particularly involved in the development of resistance. The results were further scrutinised to generate a resistome that can be analysed for their role in the development or adaptation to antibiotic resistance. Results: The 99 genes in the resistome are then compiled to create a multiple drug resistome of 25 known and novel genes identified to play a part in antibiotic resistance. The inclusion of agr genes and associated virulence factors in the identified resistome supports the role of agr quorum sensing system in multiple drug resistance. In addition, enrichment analysis also identified the kyoto encyclopedia of genes and genomes (KEGG) pathways – quorum sensing and two-component system pathways – in the resistome gene set. Conclusion: Further studies on understanding the role of the identified molecular targets such as SAA6008_00181, SAA6008_01127, agrA, agrC and coa in adapting to the pressure of antibiotics at sub-inhibitory concentrations can help in learning the molecular mechanisms causing resistance to the pathogens as well as finding other potential therapeutics.

Antibiotic-resistant Enterobacteriaceae in healthy gut flora: A report from north Indian semiurban community

Background & objectives: Rampant use of ?-lactam antibiotics in both community and hospitals has transformed the human healthy intestinal gut flora into a reservoir of antibiotic-resistant organisms. This study was conducted to find the faecal presence of antibiotic-resistant Enterobacteriaceae in faecal samples in the community in north India. Methods: In this prospective study, 207 stool samples were collected from apparently healthy individuals residing in a semiurban community in Chandigarh, India, from August to October, 2015. Isolates belonging to family Enterobacteriaceae were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and antibiotic susceptibility was determined using Clinical Laboratory Standard Institute disc diffusion method. Detection of extended spectrum ?-lactamases (TEM, SHV, OXA-1, CTXM 1, CTXM 2, CTXM 9 and CTXM 8/25), carbapenemases (IMP, VIM and KPC) and New Delhi metallo-?-lactamase was done by multiplex PCR. Results: Of the population studied, 55.5 per cent were females and 60 per cent were illiterate or had only primary education; 43.4 per cent individuals were aged <20 yr. Overall, 70.5 per cent of stool samples had antibiotic-resistant isolates. Maximum resistance was seen for cephalosporins (60.4%) followed by fluoroquinolones (41.5%). The multidrug-resistant (MDR) isolates were 2.4 per cent. The most commonly detected genes were TEM, SHV, OXA-1, CTXM-1, CTXM-2, CTXM-9 and CTXM-8/25 ?-lactamases. Escherichia coli was the most common resistant isolate, and TEM was the most common gene detected. Interpretation & conclusions: Overall, 70.5 per cent members of Enterobacteriaceae had antibiotic resistance in the community and 2.4 per cent were MDR. Higher resistance rates were observed for most commonly used drugs such as cephalosporins and fluoroquinolones. High rate of antibiotic-resistant Enterobacteriaceae in gut of healthy individuals points towards the need for active screening and prevention of dissemination.

Antibiotic Treatment Drives the Diversification of the Human Gut Resistome / 基因组蛋白质组与生物信息学报·英文版

Despite the documented antibiotic-induced disruption of the gut microbiota, the impact of antibiotic intake on strain-level dynamics, evolution of resistance genes, and factors influencing resistance dissemination potential remains poorly understood. To address this gap we analyzed public metagenomic datasets from 24 antibiotic treated subjects and controls, combined with an in-depth prospective functional study with two subjects investigating the bacterial community dynamics based on cultivation-dependent and independent methods. We observed that short-term antibiotic treatment shifted and diversified the resistome composition, increased the average copy number of antibiotic resistance genes, and altered the dominant strain genotypes in an individual-specific manner. More than 30% of the resistance genes underwent strong differentiation at the single nucleotide level during antibiotic treatment. We found that the increased potential for horizontal gene transfer, due to antibiotic administration, was ∼3-fold stronger in the differentiated resistance genes than the non-differentiated ones. This study highlights how antibiotic treatment has individualized impacts on the resistome and strain level composition, and drives the adaptive evolution of the gut microbiota.

Antibiotic resistome in farm animals and their related environments: a review / 生物工程学报

Overuse of antibiotics in livestock farming has enriched antibiotic-resistant genes as well as resistant bacteria in farm animals and their related environments. These antibiotic-resistant genes can spread to the natural environments by horizontal gene transfer and even to the food chain, posing a serious threat to the ecological environment, food safety and human health. With the development of genomic technology, the diversity and ecological distribution of antibiotic-resistant genes in farm animals and their related environments have been recently revealed. Here we summarized the research progress on antibiotic resistance genes in related fields, potential influence on human health, and future research needs.

Análisis genómico del resistoma de la cepa de Acinetobacter baumannii ABIBUN 107m multi-resistente y persistente en hospitales colombianos / Genomic analysis of the resistome of the strain of Acinetobacter baumannii ABIBUN 107m multi-resistant and persistent in colombian hospitals

Acinetobacter baumannii es una bacteria, causante de infecciones asociadas a la atención en salud como neumonía, septicemia, meningitis e infecciones urinarias entre otras. Se caracteriza por su capacidad para desarrollar y acumular rápidamente una gran variedad de mecanismos de resistencia a antibióticos. En esta investigación se realizó el análisis genómico de una cepa de A. baumannii ABIBUN 107m que forma parte de un clon persistente en hospitales colombianos, resistente a los antibióticos carbapenémicos (imipenem y meropenem), antibióticos de elección en el tratamiento infecciones causadas por este microorganismo. El genoma de esta bacteria fue secuenciado utilizando técnicas de alto rendimiento, ensamblado y anotado, obteniéndose un genoma constituido por 3954000 pb con 56 contigs; consta de 4256 genes con un tamaño promedio de 912 pb; 3796 CDS de los cuales por anotación 2884 se asignaron a COG; 57 tRNA y un porcentaje de GC de 38,74%. A. baumannii ABIBUN 107m es resistente a β-lactámicos, aminoglicósidos, quinolonas, tetraciclina, sulfonamida y colistina. En su genoma se localizaron genes asociados con el perfil de resistencia ya que presenta serin β-lactamasas (blaADC-38, blaOXA-64, blaOXA-23, bla ampC-like, bla amp(H)-like), metalo β-lactamasa_B; proteínas de unión a penicilina de elevada masa molecular, secuencias de inserción tipo ISAba1; mutaciones en los genes de DNA girasa y topoisomerasa IV subunidad A (gyrA y parC); enzimas modificadoras de aminoglicósidos (aphA-like, aad -like); cloranfenicol aciltransferasa (cat) y dehidropteroato sintasa (sul-1). Se identificaron genes pertenecientes a cinco familias de sistemas de eflujo (RND, MATE, MSF, ATP, SMR).

Acinetobacter baumannii is a bacterium causing health care associated infections such as pneumonia, septicemia, meningitis and urinary infections amongst others. It has great capacity to quickly develop and gather a big variety of drug resistance mechanisms. In this research, the genome of strain A. baumannii ABIBUN 107m was analyzed wich forms part of a persistent clon in Colombian hospitals and it’s also resistant to carbapenems (imipenem and meropenem), which are the election antibiotics for treatment of infections caused by this microorganism. The genome was sequenced using high performance technology, assembled and annotated. As a result, we obtained a 3954000 bp genome, with 56 contigs; 4256 genes with average size of 912 bp; 3796 CDS; 2884 were assigned to COG; 57 tRNA and GC percentage of 38,74%. The A. baumannii strain ABIBUN 107m, is resistant to the following antibiotic groups: β-lactams, aminoglycosides, quinolones, tetracycline, sulfonamide and colistin. Genes associated with this resistance profile were found in A. baumannii ABIBUN 107m genome serino β-lactamases (blaADC-38, blaOXA-64, blaOXA-23, bla ampC-like, bla amp(H)-like), metallo β-lactamase_B; High Molecular Mass penicillin binding proteins, ISAba1 type insertion sequences, mutations of DNA gyrase and topoisomerase IV subunit A (gyrA and parC); aminoglycoside modifying enzymes (aphA-like, aadA-like); choramphenicol acyltransferase (cat) and dehydropteroate synthase (sul-1). Genes belonging to five different efflux systems were identified (RND, MATE, MSF, ATP, SMR).