scholarly journals Zinc can counteract selection for ciprofloxacin resistance

2019 ◽  
Author(s):  
Michiel Vos ◽  
Louise Sibleyras ◽  
Lai Ka Lo ◽  
Elze Hesse ◽  
William Gaze ◽  
...  

AbstractAntimicrobial resistance (AMR) has emerged as one of the most pressing global threats to public health. AMR evolution occurs in the clinic but also in the environment, where low concentrations of antibiotics and heavy metals can respectively select and co-select for resistance. While the selective potential for AMR of both antibiotics and metals is increasingly well-characterized, studies exploring the combined effect of both types of selective agents are rare. It has previously been demonstrated that fluoroquinolone antibiotics such as ciprofloxacin can chelate metal ions. To investigate how ciprofloxacin resistance is affected by the presence of metals, we quantified selection dynamics between a ciprofloxacin-susceptible and an isogenic ciprofloxacin-resistant Escherichia coli MG1655 strain across a gradient of ciprofloxacin concentrations in the presence and absence of Zinc cations (Zn2+). The minimal selective concentration (MSC) for ciprofloxacin resistance significantly increased up to 5-fold in the presence of Zn2+. No such effect on the MSC was found for gentamicin, an antibiotic not known to chelate zinc cations. Environmental pollution usually consists of complex mixtures of antimicrobial agents. Our findings highlight the importance of taking antagonistic as well as additive or synergistic interactions between different chemical compounds into account when considering their effect on bacterial resistance evolution.Graphical abstractOne sentence summaryThe minimal selective concentration for a ciprofloxacin resistant E. coli strain increases up to 5-fold in the presence of Zinc cations.

2020 ◽  
Vol 367 (3) ◽  
Author(s):  
Michiel Vos ◽  
Louise Sibleyras ◽  
Lai Ka Lo ◽  
Elze Hesse ◽  
William Gaze ◽  
...  

ABSTRACT Antimicrobial resistance (AMR) has emerged as one of the most pressing threats to public health. AMR evolution occurs in the clinic but also in the environment, where antibiotics and heavy metals can select and co-select for AMR. While the selective potential of both antibiotics and metals is increasingly well-characterized, experimental studies exploring their combined effects on AMR evolution are rare. It has previously been demonstrated that fluoroquinolone antibiotics such as ciprofloxacin can chelate metal ions. To investigate how ciprofloxacin resistance is affected by the presence of metals, we quantified selection dynamics between a ciprofloxacin-susceptible and a ciprofloxacin-resistant Escherichia coli strain across a gradient of ciprofloxacin concentrations in presence and absence of zinc. The presence of zinc reduced growth of both strains, while ciprofloxacin inhibited exclusively the susceptible one. When present in combination zinc retained its inhibitory effect, while ciprofloxacin inhibition of the susceptible strain was reduced. Consequently, the minimal selective concentration for ciprofloxacin resistance increased up to five-fold in the presence of zinc. Environmental pollution usually comprises complex mixtures of antimicrobial agents. In addition to the usual focus on additive or synergistic interactions in complex selective mixtures, our findings highlight the importance of antagonistic selective interactions when considering resistance evolution.


2021 ◽  
Author(s):  
Jay Wook Joong Kim ◽  
Vincent Blay ◽  
Portia Mira ◽  
Miriam Barlow ◽  
Manel Camps

Fluoroquinolones are one of the most widely used class of antibiotics. They target two type II topoisomerase enzymes: gyrase and topoisomerase IV. Resistance to these drugs, which is largely caused by mutations in their target enzymes, is on the rise and becoming a serious public health risk. In this work, we analyze the sequences of 352 extraintestinal E. coli clinical isolates to gain insights into the selective pressures shaping the type II topoisomerase mutation landscape in E. coli. We identify both Quinolone Resistance-Determining Region (QRDR) and non-QRDR mutations, outline their mutation trajectories, and show that they are likely driven by different selective pressures. We confirm that ciprofloxacin resistance is specifically and strongly associated with QRDR mutations. By contrast, non-QRDR mutations are associated with the presence of the chromosomal version of ccdAB, a toxin-antitoxin operon, where the toxin CcdB is known to target gyrase. We also find that ccdAB and the evolution of QRDR mutation trajectories are partially incompatible. Finally, we identify partial deletions in CcdB and additional mutations that likely facilitate the compatibility between the presence of the ccdAB operon and QRDR mutations. These "permissive" mutations are all found in ParC (a topoisomerase IV subunit). This, and the fact that CcdB-selected mutations frequently map to topoisomerase IV, strongly suggests that this enzyme (in addition to gyrase) is likely a target for the toxin CcdB in E. coli, although an indirect effect on global supercoiling cannot be excluded. This work opens the door for the use of the presence of ccdB and of the proposed permissive mutations in the genome as genetic markers to assess the risk of quinolone resistance evolution and implies that certain strains may be genetically more refractory to evolving quinolone resistance through mutations in target enzymes.


2000 ◽  
Vol 38 (11) ◽  
pp. 3971-3978 ◽  
Author(s):  
David L. Wilson ◽  
Sheila R. Abner ◽  
Thomas C. Newman ◽  
Linda S. Mansfield ◽  
John E. Linz

Fluoroquinolones are one class of antimicrobial agents commonly used to treat severe Campylobacter jejuni infection.C. jejuni strains resistant to high levels of the fluoroquinolone ciprofloxacin (MIC ≥16 μg/ml) have been predominantly characterized with a C→T transition in codon 86 ofgyrA. The gyrA gene encodes one subunit of DNA gyrase, which is a primary target for fluoroquinolone antibiotics. This study establishes a rapid PCR-based TaqMan method for identifying ciprofloxacin-resistant C. jejuni strains that carry the C→T transition in codon 86 of gyrA. The assay uses real-time detection, eliminating the need for gel electrophoresis. Optimization of the assay parameters using purified Campylobacter DNA resulted in the ability to detect femtogram levels of DNA. The method should be useful for monitoring the development of ciprofloxacin resistance in C. jejuni. Compiled nucleotide sequence data on the quinolone resistance-determining region of gyrA inCampylobacter indicate that sequence comparison of this region is a useful method for tentative identification ofCampylobacter isolates at the species level.


2010 ◽  
Vol 54 (3) ◽  
pp. 1173-1178 ◽  
Author(s):  
Li-Yang Hsu ◽  
Thean-Yen Tan ◽  
Vincent H. Tam ◽  
Andrea Kwa ◽  
Dale Andrew Fisher ◽  
...  

ABSTRACT A surveillance study was performed in four Singapore public hospitals from 2006 to 2008 to determine the correlation between antibiotic prescription and Gram-negative bacterial antimicrobial resistance. Targeted organisms included ceftriaxone- and ciprofloxacin-resistant Escherichia coli and Klebsiella pneumoniae, as well as imipenem-resistant Pseudomonas aeruginosa and Acinetobacter spp. Antibiotic prescription data were collated in the WHO anatomical therapeutic chemical (ATC)/defined daily dose (DDD) format, while antibiotic resistance was expressed as incidence density adjusted for total inpatient-days every quarter. Individual trends were determined by linear regression, while possible associations between antibiotic prescription and resistance were evaluated via cross-correlation analysis. Results over 3 years indicated significantly rising incidence densities of ceftriaxone- and ciprofloxacin-resistant E. coli and imipenem-resistant Acinetobacter spp. (blood isolates only). Antimicrobial-resistant Klebsiella pneumoniae rates declined. The prescription rates of piperacillin-tazobactam, ertapenem, meropenem, ciprofloxacin, and levofloxacin increased significantly, while imipenem and moxifloxacin prescription decreased. Cross-correlation analysis demonstrated possible associations between prescription of fluoroquinolones and ciprofloxacin-resistant E. coli (R 2 = 0.46), fluoroquinolones and ceftriaxone-resistant E. coli (R 2 = 0.47), and carbapenems and imipenem-resistant Acinetobacter spp. (R 2 = 0.48), all at zero time lag. Changes in meropenem prescription were associated with a similar trend in imipenem-resistant Acinetobacter blood isolates after a 3-month time lag. No correlation was found between cephalosporin use and resistance. In conclusion, our data demonstrated correlation between prescription of and Gram-negative bacterial resistance to several, but not all, key antimicrobial agents in Singapore hospitals. In areas where Gram-negative bacterial resistance is endemic and prescription of broad-spectrum antimicrobial agents is high, factors other than antimicrobial usage may be equally important in maintaining high resistance rates.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Mude Shecho ◽  
Naod Thomas ◽  
Jelalu Kemal ◽  
Yimer Muktar

A cross-sectional study was carried out to determine antimicrobial drug resistance patterns of E. coli O157:H7 isolates and estimate the level of the pathogen. A total of 194 cloacae swab samples were collected randomly in two poultry farms. Standard cultural, biochemical, and serological (latex agglutination) methods were used to isolate E. coli O157:H7. The isolates were subjected to antimicrobial susceptibility testing using disc diffusion method. Out of 194 cloacae samples examined, 13.4% (n=26) were found to be positive for E. coli O157:H7. The finding indicated differences in E. coli O157:H7 infection among the different risk factors. Chicken from Adele Poultry Farm showed higher E. coli O157:H7 infection (OR = 3.89) than Haramaya University poultry farm and young birds had more infection (OR = 4.62) than adult birds. Of the total 14 antimicrobials included in the panel of study, the susceptibility results were varied with 96.15% and 0% E. coli O157:H7 isolates expressing resistance to erythromycin, clindamycin, spectinomycin, and ciprofloxacin, respectively. Multidrug resistance to more than two antimicrobial agents was detected in 24 (92.30%) of the isolates. The study showed high presence of antimicrobial resistant isolates of E. coli O157:H7. Further study is required to better understand the ecology and evolution of bacterial resistance to antimicrobial agents.


2021 ◽  
Author(s):  
Anamaria Babosan ◽  
David Skurnik ◽  
Anaëlle Muggeo ◽  
Gerald Pier ◽  
Thomas Jové ◽  
...  

The plasmid-mediated quinolone resistance (PMQR) genes have been shown to promote high level bacterial resistance to fluoroquinolone antibiotics, potentially leading to clinical treatment failures. In Escherichia coli, sub-inhibitory concentrations (sub-MIC) of the widely used fluoroquinolones are known to induce the SOS response. Interestingly, the expression of several PMQR qnr genes is controlled by the SOS master regulator. During the characterization of a small qnrD-plasmid carried in E. coli, we observed that the aminoglycosides become able to induce the SOS response in this species, thus leading to the transcription of qnrD. We found that induction of the SOS response is due to nitric oxide (NO) accumulation in presence of sub-MIC of aminoglycosides. We demonstrated that the NO accumulation is driven by two plasmid genes, ORF3 and ORF4, whose products act at two levels. ORF3 encode a FAD-binding oxidoreductase which helps NO synthesis, while ORF4 code for an FNR-type transcription factor, related to an O2-responsive regulator of hmp expression, able to repress the Hmp-mediated NO detoxification pathway of E. coli. Thus, this discovery, that other major classes of antibiotics may induce the SOS response could have worthwhile implications for antibiotic stewardship efforts in preventing the emergence of resistance.


Author(s):  
Nor Fadhilah Kamaruzzaman ◽  
Shamsaldeen Saeed

Abstract:Salmonella species (spp) and Escherichia coli (E. coli) are the most common infectious pathogens in poultry. Antimicrobials were given either for the treatment or growth promoters that can increase the possibility of emergence of bacterial resistance towards antimicrobials. The aim of this study was to determine the prevalence of antimicrobial resistant (AMR) Salmonella spp and E. coli isolated from a sample of broiler farms in East Coast Malaysia from 2018-2019. A total of 384 cloacal swabs were collected from broilers farms in Kelantan, Terengganu, and Pahang. The bacteria were isolated and confirmed by bacteriological and serological methods. Following that, confirmed isolates were subjected to antimicrobial susceptibility test. Salmonella spp and E. coli were recovered from the cloacal swabs samples with the overall prevalence of 6.5% and 51.8% respectively. In Kelantan, Terengganu and Pahang, the prevalence of Salmonella spp were 7%, 6.5% and 5.8% respectively, while the prevalence for E. coli were 50%, 48.3% and 58% respectively. Salmonella spp and E. coli displayed resistance towards the following antimicrobials: erythromycin (100% for both pathogens), chloramphenicol (76.2%, 84.5%), tetracycline (62%, 94.6%), ampicillin (47.7%, 87%), sulfamethoxazole/trimethoprim (42.9%, 83.3%), ciprofloxacin (4.8%, 23.8%), nalidixic acid (9.6%, 60.7%), streptomycin (19%,66%), and kanamycin (28.6%,57%), cephalotin (0%, 11%), gentamicin (0%, 20.2%) respectively. No resistance were recorded towards colistin for both pathogens. Multidrug resistance (MDR) was recorded in 82% of Salmonella spp and 100% of E. coli. These findings demonstrate the high prevalence of MDR Salmonella spp. and E. coli in broiler farms in East coast Malaysia. This could be attributed to the excessive use of antimicrobial agents by the poultry farm owners. Enhanced control measures and a strong monitoring system should be urgently implemented to reduce the emergence of antimicrobial resistance that is harmful to public health.


2020 ◽  
Author(s):  
lei tian ◽  
zhen zhang ◽  
ziyong sun

Abstract Background Bloodstream infections (BSIs) are a common consequence of infectious diseases and cause high morbidity and mortality. Appropriate antibiotic use is critical for patients’ treatment and prognosis. Long-term monitoring and analyzing of bacterial resistance are important for guiding physicians in choosing the appropriate antibiotics and understanding the changes in bacterial resistance and infection control. Here, we report a retrospective study on antimicrobial resistance in BSI-associated pathogens.Methods Data from the Hubei Province Antimicrobial Resistance Surveillance System (HBARSS) from 1998–2017 were retrospectively analyzed using WHONET 5.6 software. Results Data from HBARSS (1998–2017) revealed that 40,518 Gram-positive bacteria and 26,568 Gram-negative bacteria caused BSIs, the most common of which were Staphylococcus aureus and Escherichia coli. Drug susceptibility data showed that the resistance rates of E. coli and Klebsiella pneumoniae to cefotaxime were significantly higher than those to ceftazidime. Carbapenem-resistant (CR) E. coli and K. pneumoniae have also emerged. In 2013–2017, K. pneumoniae showed resistance levels reaching 15.8% and 17.5% to imipenem and meropenem, respectively, and Acinetobacter baumannii showed high resistance rates ranging from 60–80% to common antibiotics. Control of methicillin-resistant Staphylococcus aureus (MRSA) remains a major challenge, and in 2009–2017, the MRSA detection rate was 40–50%. Conclusions Prevalence of CR K. pneumoniae has increased significantly in recent years. Resistance rates of A. baumannii to common antimicrobial agents have increased exponentially, reaching high levels. MRSA remains a challenge to control.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Esther Baltazar-Encarnación ◽  
Carlos E. Escárcega-González ◽  
Ximena G. Vasto-Anzaldo ◽  
María Elena Cantú-Cárdenas ◽  
J. Rubén Morones-Ramírez

Finding novel antibiotics and antimicrobial materials has become of great importance to modern society due to the alarming increase in the development of multidrug resistance in various bacterial strains. This problem is even more complex when infections involve bacterial strains in stationary metabolic states, since most of the antibiotics found in the market do not have an effect on bacteria in dormant metabolic states. A promising field to aid in the solution of this problem is nanotechnology, since it offers a wide avenue for the development of potential therapeutics, specifically the use of silver metal nanoparticles. Silver nanoparticles have proven to be highly effective antimicrobial agents and excellent candidates to be engineered and designed into clever delivery systems, taking advantage of their rapid and potent toxicity on prokaryotic cells at low concentrations. Metal nanoparticles are most commonly synthetized through one or a series of redox chemical reactions using powerful but environmentally toxic-reducing agents. Therefore, in this work, we propose a biosynthesis method that allows the production of nanoparticles, with homogenous shapes and narrow size distributions, through an environmentally friendly technique that does not produce toxic residues. Here, silver nanoparticles were produced from silver salt (AgNO3) using three different growth culture media residues from E. coli top 10. The three different culture media residues used included LB, LBN, and LBE; all of them displaying a different chemical and nutrient composition. Here, after characterization of the different silver nanoparticles produced with the different media, we demonstrated that the LB culture-conditioned media was the most suitable to produce them since they displayed the most narrow size distribution, with an average 10.6 nm in diameter, a relatively low standard deviation of 5.5 nm, and a narrow UV-vis spectrum absorption peak at 420 nm. The other methods presented larger nanoparticle sizes and broader size distributions. Furthermore, nanoparticles produced with LB Lennox were found to be, at very low concentrations, effective antimicrobial agent against E. coli top 10 at stationary phase. Therefore, these results seem to contribute knowledge linked to the production of antimicrobial nanoparticles (Ag-NPs) through green synthesis and represent a platform to treat infections caused by nongrowing bacteria.


Author(s):  
Katarzyna Ćwiek ◽  
Anna Woźniak-Biel ◽  
Magdalena Karwańska ◽  
Magdalena Siedlecka ◽  
Christine Lammens ◽  
...  

Abstract Background A plasmid-mediated mechanism of bacterial resistance to polymyxin is a serious threat to public health worldwide. The present study aimed to determine the occurrence of plasmid-mediated colistin resistance genes and to conduct the molecular characterization of mcr-positive Escherichia coli strains isolated from Polish poultry. Methods In this study, 318 E. coli strains were characterized by the prevalence of mcr1–mcr5 genes, antimicrobial susceptibility testing by minimal inhibitory concentration method, the presence of antimicrobial resistance genes was screened by PCR, and the biofilm formation ability was tested using the crystal violet staining method. Genetic relatedness of mcr-1-positive E. coli strains was evaluated by multilocus sequence typing method. Results Among the 318 E. coli isolates, 17 (5.35%) harbored the mcr-1 gene. High antimicrobial resistance rates were observed for ampicillin (100%), tetracycline (88.24%), and chloramphenicol (82.35%). All mcr-1-positive E. coli strains were multidrug-resistant, and as many as 88.24% of the isolates contained the blaTEM gene, tetracycline (tetA and tetB), and sulfonamide (sul1, sul2, and sul3) resistance genes. Additionally, 41.18% of multidrug-resistant, mcr-1-positive E. coli isolates were moderate biofilm producers, while the rest of the strains showed weak biofilm production. Nine different sequence types were identified, and the dominant ST was ST93 (29.41%), followed by ST117 (17.65%), ST156 (11.76%), ST 8979 (11.76%), ST744 (5.88%), and ST10 (5.88%). Moreover, the new ST was identified in this study. Conclusions Our results showed a low occurrence of mcr-1-positive E. coli strains isolated from Polish poultry; however, all the isolated strains were resistant to multiple antimicrobial agents and were able to form biofilms at low or medium level.


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