scholarly journals Emerging patterns of plasmid-host coevolution that stabilize antibiotic resistance

2017 ◽  
Author(s):  
Thibault Stalder ◽  
Linda M. Rogers ◽  
Chris Renfrow ◽  
Hirokazu Yano ◽  
Zachary Smith ◽  
...  

ABSTRACTMultidrug resistant bacterial pathogens have become a serious global human health threat, and conjugative plasmids are important drivers of the rapid spread of resistance to last-resort antibiotics. Whereas antibiotics have been shown to select for adaptation of resistance plasmids to their new bacterial hosts, orvice versa, a general evolutionary mechanism has not yet emerged. Here we conducted an experimental evolution study aimed at determining general patterns of plasmid-bacteria evolution. Specifically, we found that a large conjugative resistance plasmid follows the same evolutionary trajectories as its non-conjugative mini-replicon in the same and other species. Furthermore, within a single host–plasmid pair three distinct patterns of adaptive evolution led to increased plasmid persistence: i) mutations in the replication protein gene (trfA1); ii) the acquisition by the resistance plasmid of a transposon from a co-residing plasmid encoding a putative toxin-antitoxin system; iii) a mutation in the host’s global transcriptional regulator genefur. Since each of these evolutionary solutions individually have been shown to increase plasmid persistence in other plasmid-host pairs, our work points towards common mechanisms of plasmid stabilization. These could become the targets of future alternative drug therapies to slow down the spread of antibiotic resistance.

2018 ◽  
Vol 52 (19) ◽  
pp. 11132-11141 ◽  
Author(s):  
Bing Li ◽  
Yong Qiu ◽  
Jing Zhang ◽  
Xia Huang ◽  
Hanchang Shi ◽  
...  

Author(s):  
Guoying Wang ◽  
Guo Zhao ◽  
Xiaoyu Chao ◽  
Longxiang Xie ◽  
Hongju Wang

Klebsiella pneumoniae is an important gram-negative opportunistic pathogen that causes a variety of infectious diseases, including urinary tract infections, bacteremia, pneumonia, and liver abscesses. With the emergence of multidrug-resistant (MDR) and hypervirulent K. pneumoniae (hvKP) strains, the rapid spread of these clinical strains in geography is particularly worrying. However, the detailed mechanisms of virulence and antibiotic resistance in K. pneumoniae are still not very clear. Therefore, studying and elucidating the pathogenic mechanisms and drug resistance mechanism of K. pneumoniae infection are important parts of current medical research. In this paper, we systematically summarized the virulence, biofilm, and antibiotic tolerance mechanisms of K. pneumoniae, and explored the application of whole genome sequencing and global proteomics, which will provide new clues for clinical treatment of K. pneumoniae.


2020 ◽  
Vol 70 (12) ◽  
pp. 4287-4294

Cancer is the second leading cause of death in Romania and worldwide. Cancer patients are at increasing risk of acquiring bacterial infection with multi-resistant germs, including multidrug-resistant (MDR) strains of Gram-negative bacteria involved in nosocomial infection. Romania is one of the South-Eastern European countries with one of the highest prevalence rates of MDR pathogens. To determine the resistance pattern of bacterial profile and antibiotic resistance pattern in cancer patients admitted at the County Emergency Clinical Hospital Craiova, Romania. A retrospective study of bacterial pathogens was carried out on 90 adult cancer patients admitted from January to December 2018. The analysis of the resistance patterns for the action of the appropriate antibiotics was performed using Vitek 2 Compact system and diffusion method. In this study there were analysed 92 samples from 90 oncological patients (37-86 years). A total of 157 bacterial isolates were obtained, of which 37 strains of Staphylococcus aureus (23.56%), followed by Streptococcus pneumoniae (23- 14.64%), Klebsiella spp. and Escherichia coli (22 - 14,01%). The most common isolates were from respiratory tract (86 isolates - 54.77%). High rates of MDR were found for E. coli (63.63%), MRSA (61,11%) and Klebsiella spp. (54,54%), while one third of the isolated strains of Pseudomonas aeruginosa, Acinetobacter spp. and Proteus spp. were MDR. The findings of this study may be the basis for further more extensive studies highlighting the germs involved in the infectious pathology of cancer patients, in order to determine the antimicrobial resistance and to improve the methods of prophylaxis and treatment. Keywords: multidrug resistance (MDR), cancer patients, bacterial pathogen


2020 ◽  
Vol 20 (2) ◽  
pp. 160-166
Author(s):  
Seyedeh Hanieh Eshaghi Zadeh ◽  
Hossein Fahimi ◽  
Fatemeh Fardsanei ◽  
Mohammad Mehdi Soltan Dallal

Background: Salmonellosis is a major food-borne disease worldwide. The increasing prevalence of antimicrobial resistance among food-borne pathogens such as Salmonella spp. is concerning. Objective: The main objective of this study is to identify class 1 integron genes and to determine antibiotic resistance patterns among Salmonella isolates from children with diarrhea. Methods: A total of 30 Salmonella isolates were recovered from children with diarrhea. The isolates were characterized for antimicrobial susceptibility and screened for the presence of class 1 integron genes (i.e. intI1, sulI1, and qacEΔ1). Results: The most prevalent serotype was Enteritidis 36.7%, followed by Paratyphi C (30%), and Typhimurium (16.7%). The highest rates of antibiotic resistance were obtained for nalidixic acid (53.3%), followed by streptomycin (40%), and tetracycline (36.7%). Regarding class 1 integrons, 36.7%, 26.7%, and 33.3% of the isolates carried intI1, SulI, and qacEΔ1, respectively, most of which (81.8%) were multidrug-resistant (MDR). Statistical analysis revealed that the presence of class 1 integron was significantly associated with resistance to streptomycin and tetracycline (p = 0.042). However, there was no association between class 1 integron and other antibiotics used in this study (p > 0.05). Conclusion: The high frequency of integron class 1 gene in MDR Salmonella strains indicates that these mobile genetic elements are versatile among different Salmonella serotypes, and associated with reduced susceptibility to many antimicrobials.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S179-S180
Author(s):  
Thana Khawcharoenporn ◽  
Pimjira Kanoktipakorn

Abstract Background Data existing on effectiveness of antibiotic prophylaxis (AP) for transurethral resection of the prostate (TURP) are limited in the era of antibiotic resistance. Methods A 4-year prospective observational cohort study was conducted among patients undergoing TURP in an academic tertiary-care hospital during 2016–2019. Patients were excluded if pre-operative (pre-op) urine cultures were not sent or grew mixed (>2) organisms, or they had pre-op urinary tract infection (UTI) or lost follow-up after TURP. Appropriateness of AP was defined as 1) correct dosing and duration and narrowest spectrum according to the hospital AP guidelines and local epidemiology and 2) being active against uropathogens isolated from the pre-op culture. Primary outcome was the rate of UTI within 30 days post TURP compared between appropriate antibiotic prophylaxis (AAP) and inappropriate antibiotic prophylaxis (IAP) groups. Results 342 patients were screened and 61 were excluded. Of the 281 patients included, 139 (49%) received AAP and 142 (51%) received IAP. The reasons for IAP were prescribing too broad-spectrum antibiotics (57%), inactive antibiotics (41%) and incorrect dosing (2%). Pre-op urine cultures were no growth in 148 patients (53%). Among the 133 positive urine cultures with 144 isolates, Escherichia coli (52%) was the most commonly isolated. Thirty-one percent of these 144 isolates produced extended-spectrum beta-lactamase (ESBL) and 23 (16%) isolates were multidrug-resistant. The resistant rates of Enterobacteriaceae were 73% for ciprofloxacin, 65% for TMP-SMX and 46% for ceftriaxone. The two most commonly prescribed prophylactic antibiotics were ceftriaxone (51%) and ciprofloxacin (34%). The rate of UTI within 30 days post-TURP was significantly higher in IAP group compared to AAP group (47% vs 27%; P< 0.001). Prescribing inactive prophylactic antibiotics was the independent factor associated with 30-day post-TURP UTI (adjusted odds ratio 2.88; P=0.001). Conclusion Appropriate antibiotic prophylaxis significantly reduced UTI within 30 days of elective TURP. Obtaining pre-op urine culture and prescribing an active prophylactic agent are critical for preventing post-TURP UTI in the era of antibiotic resistance. Disclosures All Authors: No reported disclosures


2021 ◽  
Vol 9 (7) ◽  
pp. 1468
Author(s):  
Gavin J. Fenske ◽  
Joy Scaria

Salmonella enterica is common foodborne pathogen that generates both enteric and systemic infections in hosts. Antibiotic resistance is common is certain serovars of the pathogen and of great concern to public health. Recent reports have documented the co-occurrence of metal resistance with antibiotic resistance in one serovar of S. enterica. Therefore, we sought to identify possible co-occurrence in a large genomic dataset. Genome assemblies of 56,348 strains of S. enterica comprising 20 major serovars were downloaded from NCBI. The downloaded assemblies were quality controlled and in silico serotyped to ensure consistency and avoid improper annotation from public databases. Metal and antibiotic resistance genes were identified in the genomes as well as plasmid replicons. Co-occurrent genes were identified by constructing a co-occurrence matrix and grouping said matrix using k-means clustering. Three groups of co-occurrent genes were identified using k-means clustering. Group 1 was comprised of the pco and sil operons that confer resistance to copper and silver, respectively. Group 1 was distributed across four serovars. Group 2 contained the majority of the genes and little to no co-occurrence was observed. Metal and antibiotic co-occurrence was identified in group 3 that contained genes conferring resistance to: arsenic, mercury, beta-lactams, sulfonamides, and tetracyclines. Group 3 genes were also associated with an IncQ1 class plasmid replicon. Metal and antibiotic co-occurrence from group 3 genes is mostly isolated to one clade of S. enterica I 4,[5],12:i:-.


2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Yue Xing ◽  
Xiaoxi Kang ◽  
Siwei Zhang ◽  
Yujie Men

AbstractTo explore how co-occurring non-antibiotic environmental stressors affect evolutionary trajectories toward antibiotic resistance, we exposed susceptible Escherichia coli K-12 populations to environmentally relevant levels of pesticides and streptomycin for 500 generations. The coexposure substantially changed the phenotypic, genotypic, and fitness evolutionary trajectories, resulting in much stronger streptomycin resistance (>15-fold increase) of the populations. Antibiotic target modification mutations in rpsL and rsmG, which emerged and dominated at late stages of evolution, conferred the strong resistance even with less than 1% abundance, while the off-target mutations in nuoG, nuoL, glnE, and yaiW dominated at early stages only led to mild resistance (2.5–6-fold increase). Moreover, the strongly resistant mutants exhibited lower fitness costs even without the selective pressure and had lower minimal selection concentrations than the mildly resistant ones. Removal of the selective pressure did not reverse the strong resistance of coexposed populations at a later evolutionary stage. The findings suggest higher risks of the selection and propagation of strong antibiotic resistance in environments potentially impacted by antibiotics and pesticides.


Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 775
Author(s):  
Kezia Drane ◽  
Roger Huerlimann ◽  
Michelle Power ◽  
Anna Whelan ◽  
Ellen Ariel ◽  
...  

Dissemination of antibiotic resistance (AR) in marine environments is a global concern with a propensity to affect public health and many ecosystems worldwide. We evaluated the use of sea turtles as sentinel species for monitoring AR in marine environments. In this field, antibiotic-resistant bacteria have been commonly identified by using standard culture and sensitivity tests, leading to an overrepresentation of specific, culturable bacterial classes in the available literature. AR was detected against all major antibiotic classes, but the highest cumulative global frequency of resistance in all represented geographical sites was against the beta-lactam class by a two-fold difference compared to all other antibiotics. Wastewater facilities and turtle rehabilitation centres were associated with higher incidences of multidrug-resistant bacteria (MDRB) accounting for an average of 58% and 49% of resistant isolates, respectively. Furthermore, a relatively similar prevalence of MDRB was seen in all studied locations. These data suggest that anthropogenically driven selection pressures for the development of AR in sea turtles and marine environments are relatively similar worldwide. There is a need, however, to establish direct demonstrable associations between AR in sea turtles in their respective marine environments with wastewater facilities and other anthropogenic activities worldwide.


2021 ◽  
Vol 14 (4) ◽  
pp. 325
Author(s):  
David Sáez Moreno ◽  
Zehra Visram ◽  
Michele Mutti ◽  
Marcela Restrepo-Córdoba ◽  
Susana Hartmann ◽  
...  

Due to the rapid spread of antibiotic resistance, and the difficulties of treating biofilm-associated infections, alternative treatments for S. aureus infections are urgently needed. We tested the lytic activity of several wild type phages against a panel of 110 S. aureus strains (MRSA/MSSA) composed to reflect the prevalence of S. aureus clonal complexes in human infections. The plaquing host ranges (PHR) of the wild type phages were in the range of 51% to 60%. We also measured what we called the kinetic host range (KHR), i.e., the percentage of strains for which growth in suspension was suppressed for 24 h. The KHR of the wild type phages ranged from 2% to 49%, substantially lower than the PHRs. To improve the KHR and other key pharmaceutical properties, we bred the phages by mixing and propagating cocktails on a subset of S. aureus strains. These bred phages, which we termed evolution-squared (ε2) phages, have broader KHRs up to 64% and increased virulence compared to the ancestors. The ε2-phages with the broadest KHR have genomes intercrossed from up to three different ancestors. We composed a cocktail of three ε2-phages with an overall KHR of 92% and PHR of 96% on 110 S. aureus strains and called it PM-399. PM-399 has a lower propensity to resistance formation than the standard of care antibiotics vancomycin, rifampicin, or their combination, and no resistance was observed in laboratory settings (detection limit: 1 cell in 1011). In summary, ε2-phages and, in particular PM-399, are promising candidates for an alternative treatment of S. aureus infections.


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