The gut microbiota resistome provides development of drug resistance in causative agents of human infectious diseases

Author(s):  
Е.Н. Ильина ◽  
Е.И. Олехнович ◽  
А.В. Павленко

С течением времени подходы к изучению резистентности к антибиотикам трансформировались от сосредоточения на выделенных в виде чистой культуры патогенных микроорганизмах к исследованию резистентности на уровне микробных сообществ, составляющих биотопы человека и окружающей среды. По мере того, как продвигается изучение устойчивости к антибиотикам, возникает необходимость использования комплексного подхода для улучшения информирования мирового сообщества о наблюдаемых тенденциях в этой области. Все более очевидным становится то, что, хотя не все гены резистентности могут географически и филогенетически распространяться, угроза, которую они представляют, действительно серьезная и требует комплексных междисциплинарных исследований. В настоящее время резистентность к антибиотикам среди патогенов человека стала основной угрозой в современной медицине, и существует значительный интерес к определению ниши, в которых бактерии могут получить гены антибиотикорезистентности, и механизмов их передачи. В данном обзоре мы рассматриваем проблемы, возникшие на фоне широкого использования человечеством антибактериальных препаратов, в свете формирования микрофлорой кишечника резервуара генов резистентности. Over the time, studies of antibiotic resistance have transformed from focusing on pathogenic microorganisms isolated as a pure culture to analysis of resistance at the level of microbial communities that constitute human and environmental biotopes. Advancing studies of antibiotic resistance require an integrated approach to enhance availability of information about observed tendencies in this field to the global community. It becomes increasingly obvious that, even though not all resistance genes can geographically and phylogenetically spread, the threat they pose is indeed serious and requires complex interdisciplinary research. Currently, the antibiotic resistance of human pathogens has become a challenge to modern medicine, which is now focusing on determining a potential source for bacterial genes of drug resistance and mechanisms for the gene transmission. In this review, we discussed problems generated by the widespread use of antibacterial drugs in the light of forming a reservoir of resistance genes by gut microflora.

2019 ◽  
Author(s):  
Sanjeet Kumar ◽  
Kanika Bansal ◽  
Prashant P. Patil ◽  
Amandeep Kaur ◽  
Satinder Kaur ◽  
...  

ABSTRACTWe report first complete genome sequence and analysis of an extreme drug resistance (XDR) nosocomial Stenotrophomonas maltophilia that is resistant to the mainstream drugs i.e. trimethoprim/sulfamethoxazole (TMP/SXT) and levofloxacin. Taxonogenomic analysis revealed it to be a novel genomospecies of the Stenotrophomonas maltophilia complex (Smc). Comprehensive genomic investigation revealed fourteen dynamic regions (DRs) exclusive to SM866, consisting of diverse antibiotic resistance genes, efflux pumps, heavy metal resistance, various transcriptional regulators etc. Further, resistome analysis of Smc clearly depicted SM866 to be an enriched strain, having diversified resistome consisting of sul1 and sul2 genes. Interestingly, SM866 does not have any plasmid but it harbors two diverse super-integrons of chromosomal origin. Apart from genes for sulfonamide resistance (sul1 and sul2), both of these integrons harbor an array of antibiotic resistance genes linked to ISCR (IS91-like elements common regions) elements. These integrons also harbor genes encoding resistance to commonly used disinfectants like quaternary ammonium compounds and heavy metals like mercury. Hence, isolation of a novel strain belonging to a novel sequence type (ST) and genomospecies with diverse array of resistance from a tertiary care unit of India indicates extent and nature of selection pressure driving XDRs in hospital settings. There is an urgent need to employ complete genome based investigation using emerging technologies for tracking emergence of XDR at the global level and designing strategies of sanitization and antibiotic regime.Impact StatementThe hospital settings in India have one of the highest usage of antimicrobials and heavy patient load. Our finding of a novel clinical isolate of S. maltophilia complex with two super-integrons harbouring array of antibiotic resistance genes along with antimicrobials resistance genes indicates the extent and the nature of selection pressures in action. Further, the presence of ISCR type of transposable elements on both integrons not only indicates its propensity to transfer resistome but also their chromosomal origin suggests possibilities for further genomic/phenotypic complexities. Such complex cassettes and strain are potential threat to global health care. Hence, there is an urgent need to employ cost-effective long read technologies to keep vigilance on novel and extreme antimicrobial resistance pathogens in populous countries. There is also need for surveillance for usage of antimicrobials for hygiene and linked/rapid co-evolution of extreme drug resistance in nosocomial pathogens. Our finding of the chromosomal encoding XDR will shed a light on the need of hour to understand the evolution of an opportunistic nosocomial pathogen belonging to S. maltophilia.RepositoriesComplete genome sequence of Stenotrophomonas maltophilia SM866: CP031058


2017 ◽  
Author(s):  
Christian Munck ◽  
Mostafa M. Hashim Ellabaan ◽  
Michael Schantz Klausen ◽  
Morten O.A. Sommer

AbstractGenes capable of conferring resistance to clinically used antibiotics have been found in many different natural environments. However, a concise overview of the resistance genes found in common human bacterial pathogens is lacking, which complicates risk ranking of environmental reservoirs. Here, we present an analysis of potential antibiotic resistance genes in the 17 most common bacterial pathogens isolated from humans. We analyzed more than 20,000 bacterial genomes and defined a clinical resistome as the set of resistance genes found across these genomes. Using this database, we uncovered the co-occurrence frequencies of the resistance gene clusters within each species enabling identification of co-dissemination and co-selection patterns. The resistance genes identified in this study represent the subset of the environmental resistome that is clinically relevant and the dataset and approach provides a baseline for further investigations into the abundance of clinically relevant resistance genes across different environments. To facilitate an easy overview the data is presented at the species level at www.resistome.biosustain.dtu.dk.


mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
Yu Pan ◽  
Jiaxiong Zeng ◽  
Liguan Li ◽  
Jintao Yang ◽  
Ziyun Tang ◽  
...  

ABSTRACT Widespread use of antibiotics has enhanced the evolution of highly resilient pathogens and poses a severe risk to human health via coselection of antibiotic resistance genes (ARGs) and virulence factors (VFs). In this study, we rigorously evaluate the abundance relationship and physical linkage between ARGs and VFs by performing a comprehensive analysis of 9,070 bacterial genomes isolated from multiple species and hosts. The coexistence of ARGs and VFs was observed in bacteria across distinct phyla, pathogenicities, and habitats, especially among human-associated pathogens. The coexistence patterns of gene elements in different habitats and pathogenicity groups were similar, presumably due to frequent gene transfer. A shorter intergenic distance between mobile genetic elements and ARGs/VFs was detected in human/animal-associated bacteria, indicating a higher transfer potential. Increased accumulation of exogenous ARGs/VFs in human pathogens highlights the importance of gene acquisition in the evolution of human commensal bacteria. Overall, the findings provide insights into the genic features of combinations of ARG-VF and expand our understanding of ARG-VF coexistence in bacteria. IMPORTANCE Antibiotic resistance has become a serious global health concern. Despite numerous case studies, a comprehensive analysis of ARG and VF coexistence in bacteria is lacking. In this study, we explore the coexistence profiles of ARGs and VFs in diverse categories of bacteria by using a high-resolution bioinformatics approach. We also provide compelling evidence of unique ARG-VF gene pairs coexisting in specific bacterial genomes and reveal the potential risk associated with the coexistence of ARGs and VFs in organisms in both clinical settings and environments.


2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
J. M. Mutua ◽  
C. G. Gitao ◽  
L. C. Bebora ◽  
F. K. Mutua

This study was designed to determine antimicrobial resistance profiles of bacteria isolated from the nasal cavity of healthy camels. A total of 255 nasal samples (swabs) were collected in Isiolo, Samburu, and Nakuru counties, Kenya, from which 404 bacterial isolates belonging to various genera and species were recovered. The bacterial isolates included Bacillus (39.60%), coagulase-negative Staphylococcus (29.95%), Streptococcus species other than Streptococcus agalactiae (25.74%), coagulase-positive Staphylococcus (3.96%), and Streptococcus agalactiae (0.74%). Isolates were most susceptible to Gentamicin (95.8%), followed by Tetracycline (90.5%), Kanamycin and Chloramphenicol (each at 85.3%), Sulphamethoxazole (84.2%), Co-trimoxazole (82.1%), Ampicillin (78.9%), and finally Streptomycin (76.8%). This translated to low resistance levels. Multidrug resistance was also reported in 30.5% of the isolates tested. Even though the antibiotic resistance demonstrated in this study is low, the observation is significant, since the few resistant normal flora could be harboring resistance genes which can be transferred to pathogenic bacteria within the animal, to other animals’ bacteria and, most seriously, to human pathogens.


2011 ◽  
Vol 77 (5) ◽  
pp. 1601-1607 ◽  
Author(s):  
Eva Raphael ◽  
Lisa K. Wong ◽  
Lee W. Riley

ABSTRACTA substantial proportion of infections caused by drug-resistant Gram-negative bacteria (GNB) in community and health care settings are recognized to be caused by evolutionarily related GNB strains. Their global spread has been suggested to occur due to human activities, such as food trade and travel. These multidrug-resistant GNB pathogens often harbor mobile drug resistance genes that are highly conserved in their sequences. Because they appear across different GNB species, these genes may have origins other than human pathogens. We hypothesized that saprophytes in common human food products may serve as a reservoir for such genes. Between July 2007 and April 2008, we examined 25 batches of prepackaged retail spinach for cultivatable GNB population structure by 16S rRNA gene sequencing and for antimicrobial drug susceptibility testing and the presence of extended-spectrum beta-lactamase (ESBL) genes. We found 20 recognized GNB species among 165 (71%) of 231 randomly selected colonies cultured from spinach. Twelve strains suspected to express ESBLs based on resistance to cefotaxime and ceftazidime were further examined forblaCTX-MandblaTEMgenes. We found a 712-bp sequence inPseudomonas teessideathat was 100% identical to positions 10 to 722 of an 876-bpblaCTX-M-15gene of anE. colistrain. Additionally, we identified newly recognized ESBLblaRAHN-2sequences fromRahnella aquatilis. These observations demonstrate that saprophytes in common fresh produce can harbor drug resistance genes that are also found in internationally circulating strains of GNB pathogens; such a source may thus serve as a reservoir for drug resistance genes that ultimately enter pathogens to affect human health.


mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
María Getino ◽  
David J. Sanabria-Ríos ◽  
Raúl Fernández-López ◽  
Javier Campos-Gómez ◽  
José M. Sánchez-López ◽  
...  

ABSTRACT Bacterial conjugation constitutes a major horizontal gene transfer mechanism for the dissemination of antibiotic resistance genes among human pathogens. Antibiotic resistance spread could be halted or diminished by molecules that interfere with the conjugation process. In this work, synthetic 2-alkynoic fatty acids were identified as a novel class of conjugation inhibitors. Their chemical properties were investigated by using the prototype 2-hexadecynoic acid and its derivatives. Essential features of effective inhibitors were the carboxylic group, an optimal long aliphatic chain of 16 carbon atoms, and one unsaturation. Chemical modification of these groups led to inactive or less-active derivatives. Conjugation inhibitors were found to act on the donor cell, affecting a wide number of pathogenic bacterial hosts, including Escherichia, Salmonella, Pseudomonas, and Acinetobacter spp. Conjugation inhibitors were active in inhibiting transfer of IncF, IncW, and IncH plasmids, moderately active against IncI, IncL/M, and IncX plasmids, and inactive against IncP and IncN plasmids. Importantly, the use of 2-hexadecynoic acid avoided the spread of a derepressed IncF plasmid into a recipient population, demonstrating the feasibility of abolishing the dissemination of antimicrobial resistances by blocking bacterial conjugation. IMPORTANCE Diseases caused by multidrug-resistant bacteria are taking an important toll with respect to human morbidity and mortality. The most relevant antibiotic resistance genes come to human pathogens carried by plasmids, mainly using conjugation as a transmission mechanism. Here, we identified and characterized a series of compounds that were active against several plasmid groups of clinical relevance, in a wide variety of bacterial hosts. These inhibitors might be used for fighting antibiotic-resistance dissemination by inhibiting conjugation. Potential inhibitors could be used in specific settings (e.g., farm, fish factory, or even clinical settings) to investigate their effect in the eradication of undesired resistances.


Author(s):  
O. C. Adekunle ◽  
A. J. Falade- Fatila ◽  
R. Ojedele ◽  
G. Odewale

The emerging drug resistance, especially among the Escherichia coli (E.coli) isolates from pregnant women, spread rapidly within the community. Urinary tract infection (UTI) is a well-known bacterial infection posing serious health problem in pregnant women. Also, multi-drug resistance is becoming rampant, and it is of serious public health concern. Treatment of E. coli is now a challenge due to continuous increase in resistance towards commonly prescribed antibiotics, thus posing a threat to treatment. Hence, the aim of the study is to determine antibiotic resistance genes in some multiple antibiotic resistant E.coli from apparently healthy pregnant women in Osun State. A cross-sectional study design was used to collect 150 mid-stream urine samples from apparently healthy pregnant women from March, 2018 to September, 2018. A well structured questionnaire and informed consent were used for data collection. Standard loop technique was used to place 0.001 ml of urine on Cysteine Lactose Electrolyte Deficient (CLED) medium, Blood agar, MacConkey agar and incubated at 37 °C for 24 h. A standard agar disc diffusion method was used to determine antimicrobial susceptibility pattern of the isolates. The molecular detection of the resistant genes was done using PCR techniques. The ages of women enrolled in this study ranges from 22 to 42 years (mean ± standard deviation = 31 ± 4.7 years). Escherichia coli showed high percentage of resistance to ampicillin and low resistance to ciprofloxacin and penicillin. All the E. coli isolates were sensitive to levofloxacin, and most were resistant to Meropenem. Multiple drug resistance was observed in all the isolates. Resistance genes in VIM 390bp, bla ctx-M 585bp and TEM 517bp were detected in some of the representative E. coli isolates profiled. This study identified the presence of Multi-drug resistance genes in E. coli associated UTI among pregnant women in Osogbo.


2019 ◽  
Author(s):  
Yiqin Deng ◽  
Haidong Xu ◽  
Youlu Su ◽  
Songlin Liu ◽  
Liwen Xu ◽  
...  

Abstract Background Horizontal gene transfer (HGT), which is affected by environmental pollution and climate change, promotes genetic communication, changing bacterial pathogenicity and drug resistance. However, few studies have been conducted on the effect of HGT on the high pathogenicity and drug resistance of the opportunistic pathogen Vibrio harveyi .Results V. harveyi 345 that was multidrug resistant and infected Epinephelus oanceolutus was isolated from a diseased organism in Shenzhen, Southern China, an important and contaminated aquaculture area. Analysis of the entire genome sequence predicted 5,678 genes including 487 virulence genes contributing to bacterial pathogenesis and 25 antibiotic-resistance genes (ARGs) contributing to antimicrobial resistance. Five ARGs ( tetm , tetb , qnrs , dfra17 , and sul2 ) and one virulence gene (CU052_28670) on the pAQU-type plasmid p345-185, provided direct evidence for HGT. Comparative genome analysis of 31 V. harveyi strains indicated that 217 genes and 7 gene families, including a class C beta-lactamase gene, a virulence-associated protein D gene, and an OmpA family protein gene were specific to strain V. harveyi 345. These genes could contribute to HGT or be horizontally transferred from other bacteria to enhance the virulence or antibiotic resistance of 345. Mobile genetic elements in 71 genomic islands encoding virulence factors for three type III secretion proteins and 13 type VI secretion system proteins, and two incomplete prophage sequences were detected that could be HGT transfer tools. Evaluation of the complete genome of V. harveyi 345 and comparative genomics indicated genomic exchange, especially exchange of pathogenic genes and drug-resistance genes by HGT contributing to pathogenicity and drug resistance. Climate change and continued environmental deterioration are expected to accelerate the HGT of V. harveyi , increasing its pathogenicity and drug resistance.Conclusion This study provides timely information for further analysis of V. harveyi pathogenesis and antimicrobial resistance and developing pollution control measurements for coastal areas.


2021 ◽  
Vol 14 (1) ◽  
pp. 85-91
Author(s):  
Momtaz A. Shahein ◽  
Amany N. Dapgh ◽  
Essam Kamel ◽  
Samah F. Ali ◽  
Eman A. Khairy ◽  
...  

Background and Aim: Camels are important livestock in Egypt on cultural and economic bases, but studies of etiological agents of camelid diseases are limited. The enteropathogen Escherichia coli is a cause of broad spectrum gastrointestinal infections among humans and animals, especially in developing countries. Severe infections can lead to death. The current study aimed to identify pathogenic E. coli strains that cause diarrhea in camel calves and characterize their virulence and drug resistance at a molecular level. Materials and Methods: Seventy fecal samples were collected from diarrheic neonatal camel calves in Giza Governorate during 2018-2019. Samples were cultured on a selective medium for E. coli, and positive colonies were confirmed biochemically, serotyped, and tested for antibiotic susceptibility. E. coli isolates were further confirmed through detection of the housekeeping gene, yaiO, and examined for the presence of virulence genes; traT and fimH and for genes responsible for antibiotic resistance, ampC, aadB, and mphA. The isolates in the important isolated serotype, E. coli O26, were examined for toxigenic genes and sequenced. Results: The bacteriological and biochemical examination identified 12 E. coli isolates from 70 fecal samples (17.1%). Serotyping of these isolates showed four types: O26, four isolates, 33.3%; O103, O111, three isolates each, 25%; and O45, two isolates, 16.7%. The isolates showed resistance to vancomycin (75%) and ampicillin (66.6%), but were highly susceptible to ciprofloxacin, norfloxacin, and tetracycline (100%). The structural gene, yaiO (115 bp), was amplified from all 12 E. coli isolates and traT and fimH genes were amplified from 10 and 8 isolates, respectively. Antibiotic resistance genes, ampC, mphA, and aadB, were harbored in 9 (75%), 8 (66.6%), and 5 (41.7%), respectively. Seven isolates (58.3%) were MDR. Real-time-polymerase chain reaction of the O26 isolates identified one isolate harboring vt1, two with vt2, and one isolate with neither gene. Sequencing of the isolates revealed similarities to E. coli O157 strains. Conclusion: Camels and other livestock suffer various diseases, including diarrhea often caused by microbial pathogens. Enteropathogenic E. coli serotypes were isolated from diarrheic neonatal camel calves. These isolates exhibited virulence and multiple drug resistance genes.


2019 ◽  
Vol 85 (22) ◽  
Author(s):  
Abigail L. Manson ◽  
Daria Van Tyne ◽  
Timothy J. Straub ◽  
Sarah Clock ◽  
Michael Crupain ◽  
...  

ABSTRACT Industrial farms are unique, human-created ecosystems that provide the perfect setting for the development and dissemination of antibiotic resistance. Agricultural antibiotic use amplifies naturally occurring resistance mechanisms from soil ecologies, promoting their spread and sharing with other bacteria, including those poised to become endemic within hospital environments. To better understand the role of enterococci in the movement of antibiotic resistance from farm to table to clinic, we characterized over 300 isolates of Enterococcus cultured from raw chicken meat purchased at U.S. supermarkets by the Consumers Union in 2013. Enterococcus faecalis and Enterococcus faecium were the predominant species found, and antimicrobial susceptibility testing uncovered striking levels of resistance to medically important antibiotic classes, particularly from classes approved by the FDA for use in animal production. While nearly all isolates were resistant to at least one drug, bacteria from meat labeled as raised without antibiotics had fewer resistances, particularly for E. faecium. Whole-genome sequencing of 92 isolates revealed that both commensal- and clinical-isolate-like enterococcal strains were associated with chicken meat, including isolates bearing important resistance-conferring elements and virulence factors. The ability of enterococci to persist in the food system positions them as vehicles to move resistance genes from the industrial farm ecosystem into more human-proximal ecologies. IMPORTANCE Bacteria that contaminate food can serve as a conduit for moving drug resistance genes from farm to table to clinic. Our results show that chicken meat-associated isolates of Enterococcus are often multidrug resistant, closely related to pathogenic lineages, and harbor worrisome virulence factors. These drug-resistant agricultural isolates could thus represent important stepping stones in the evolution of enterococci into drug-resistant human pathogens. Although significant efforts have been made over the past few years to reduce the agricultural use of antibiotics, continued assessment of agricultural practices, including the roles of processing plants, shared breeding flocks, and probiotics as sources for resistance spread, is needed in order to slow the evolution of antibiotic resistance. Because antibiotic resistance is a global problem, global policies are needed to address this threat. Additional measures must be taken to mitigate the development and spread of antibiotic resistance elements from farms to clinics throughout the world.


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