Transfer of Drug-Resistance Genes into Hematopoietic Progenitors

2002 ◽  
pp. 341-354
Author(s):  
OMER N. KOÇ ◽  
STEVEN P. ZIELSKE ◽  
JUSTIN C. ROTH ◽  
JANE S. REESE ◽  
STANTON L. GERSON
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.


BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuan Wu ◽  
Lin Yang ◽  
Wen-Ge Li ◽  
Wen Zhu Zhang ◽  
Zheng Jie Liu ◽  
...  

Abstract Background Clade 5 Clostridioides difficile diverges significantly from the other clades and is therefore, attracting increasing attention due its great heterogeneity. In this study, we used third-generation sequencing techniques to sequence the complete whole genomes of three ST11 C. difficile isolates, RT078 and another two new ribotypes (RTs), obtained from three independent hospitalized elderly patients undergoing antibiotics treatment. Mobile genetic elements (MGEs), antibiotic-resistance, drug resistance genes, and virulent-related genes were analyzed and compared within these three isolates. Results Isolates 10,010 and 12,038 carried a distinct deletion in tcdA compared with isolate 21,062. Furthermore, all three isolates had identical deletions and point-mutations in tcdC, which was once thought to be a unique characteristic of RT078. Isolate 21,062 (RT078) had a unique plasmid, different numbers of transposons and genetic organization, and harboring special CRISPR spacers. All three isolates retained high-level sensitivity to 11 drugs and isolate 21,062 (RT078) carried distinct drug-resistance genes and loss of numerous flagellum-related genes. Conclusions We concluded that capillary electrophoresis based PCR-ribotyping is important for confirming RT078. Furthermore, RT078 isolates displayed specific MGEs, indicating an independent evolutionary process. In the further study, we could testify these findings with more RT078 isolates of divergent origins.


2001 ◽  
Vol 45 (7) ◽  
pp. 1982-1989 ◽  
Author(s):  
Adriana E. Rosato ◽  
Bonnie S. Lee ◽  
Kevin A. Nash

ABSTRACT Corynebacterium jeikeium is an opportunistic pathogen primarily of immunocompromised (neutropenic) patients. Broad-spectrum resistance to antimicrobial agents is a common feature of C. jeikeium clinical isolates. We studied the profiles of susceptibility of 20 clinical strains of C. jeikeium to a range of antimicrobial agents. The strains were separated into two groups depending on the susceptibility to erythromycin (ERY), with one group (17 strains) representing resistant organisms (MIC > 128 μg/ml) and the second group (3 strains) representing susceptible organisms (MIC ≤ 0.25 μg/ml). The ERY resistance crossed to other members of the macrolide-lincosamide-streptogramin B (MLSb) group. Furthermore, this resistance was inducible with MLSb agents but not non-MLSb agents. Expression of ERY resistance was linked to the presence of an allele of the class X erm genes,erm(X)cj, with >93% identity to other ermgenes of this class. Our evidence indicates that erm(X)cj is integrated within the chromosome, which contrasts with previous reports for the plasmid-associated erm(X) genes found inC. diphtheriae and C. xerosis. In 40% ofC. jeikeium strains, erm(X)cj is present within the transposon, Tn5432. However, in the remaining strains, the components of Tn5432 (i.e., the erm and transposase genes) have separated within the chromosome. The rearrangement of Tn5432 leads to the possibility that the other drug resistance genes have become included in a new composite transposon bound by the IS1249 elements.


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


2020 ◽  
Vol 17 (12) ◽  
pp. 739-742
Author(s):  
Ningbo Liao ◽  
Clarissa A. Borges ◽  
Julia Rubin ◽  
Yuan Hu ◽  
Hector A. Ramirez ◽  
...  

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