scholarly journals Shared and Unique Evolutionary Trajectories to Ciprofloxacin Resistance in Gram-Negative Bacterial Pathogens

mBio ◽  
2021 ◽  
Author(s):  
Jaime E. Zlamal ◽  
Semen A. Leyn ◽  
Mallika Iyer ◽  
Marinela L. Elane ◽  
Nicholas A. Wong ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Experimental Evolution ◽  
Bacterial Pathogens ◽  
Genome Rearrangements ◽  
Microbial Populations ◽  
Gram Negative ◽  
Evolutionary Trajectories ◽  
Ciprofloxacin Resistance

The challenge of spreading antibiotic resistance calls for systematic efforts to develop more “irresistible” drugs based on a deeper understanding of dynamics and mechanisms of antibiotic resistance acquisition. To address this challenge, we have established a comparative resistomics approach which combines experimental evolution in a continuous-culturing device, the morbidostat, with ultradeep sequencing of evolving microbial populations to identify evolutionary trajectories (mutations and genome rearrangements) leading to antibiotic resistance over a range of target pathogens.

scholarly journals Shared and Unique Evolutionary Trajectories to Ciprofloxacin Resistance in Gram-negative Bacterial Pathogens

2021 ◽  
Author(s):  
Jaime E. Zlamal ◽  
Semen A Leyn ◽  
Mallika Iyer ◽  
Marinela Elane ◽  
Nicholas A Wong ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Target Genes ◽  
Bacterial Pathogens ◽  
Genetic Alterations ◽  
Bacterial Populations ◽  
Gram Negative ◽  
Acquired Drug Resistance ◽  
Wide Range ◽  
Evolutionary Trajectories ◽  
Ciprofloxacin Resistance

The resistance to broad-spectrum antibiotic ciprofloxacin is detected in high rates for a wide range of bacterial pathogens. To investigate dynamics of ciprofloxacin resistance development we proposed a comparative resistomics workflow for three clinically relevant species of Gram-negative bacteria: Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa. We combined experimental evolution in a morbidostat with deep sequencing of evolving bacterial populations in time series that reveals both shared and unique aspects of evolutionary trajectories patterns. Representative clone characterization by sequencing and MIC measurements enabled direct assessment of mutations impact on the extent of acquired drug resistance. In all three species we observed a two-stage evolution: (1) early ciprofloxacin resistance reaching 4-16-fold of wildtype MIC commonly as a result of single mutations in DNA gyrase target genes (gyrA or gyrB) and (2) additional genetic alterations affecting transcriptional control of drug efflux machinery or secondary target genes (DNA topoisomerase parC or parE).

scholarly journals Tell Me Where You’ve Been and I’ll Tell You How You’ll Evolve

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Marco Fumasoni
Keyword(s):  
High Temperatures ◽  
Adaptive Evolution ◽  
Experimental Evolution ◽  
Evolutionary Biology ◽  
Genetic Basis ◽  
Microbial Populations ◽  
Evolutionary Processes ◽  
Link Type ◽  
Selection Experiments ◽  
Evolutionary Trajectories

ABSTRACT The reproducibility of adaptive evolution is a long-standing debate in evolutionary biology. Kempher et al. (M. L. Kempher, X. Tao, R. Song, B. Wu, et al., mBio 11:e00569-20, 2020, https://doi.org/10.1128/mBio.00569-20) used experimental evolution to investigate the effect of previous evolutionary trajectories on the ability of microbial populations to adapt to high temperatures. Despite the divergence caused by adaptation to previous environments, all populations reproducibly converged on similar final levels of fitness. Nevertheless, the genetic basis of adaptation depended on past selection experiments, reinforcing the idea that previous adaptation can dictate the trajectories of later evolutionary processes.

scholarly journals Mutasynthetic Production and Antimicrobial Characterization of Darobactin Analogs

2021 ◽  
Vol 9 (3) ◽  
Author(s):  
Nils Böhringer ◽  
Robert Green ◽  
Yang Liu ◽  
Ute Mettal ◽  
Michael Marner ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Heterologous Expression ◽  
Bacterial Pathogens ◽  
Therapeutic Options ◽  
The Novel ◽  
Proof Of Concept ◽  
Gram Negative ◽  
Pharmacokinetic Properties

Therapeutic options to combat Gram-negative bacterial pathogens are dwindling with increasing antibiotic resistance. This study presents a proof of concept for the heterologous-expression approach to expand on the novel antibiotic class of darobactins and to generate analogs with different activities and pharmacokinetic properties.

scholarly journals Bacterial profile and their antibiotic resistance patterns from blood culture in Intensive Care Unit patients at the University Of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.

2019 ◽  
Author(s):  
Segen Tekle Gebre-egziabher ◽  
Feleke Moges Yehuala ◽  
Zemene Tigabu Kebede ◽  
Alem Getaneh Mehari
Keyword(s):  
Intensive Care Unit ◽  
Antibiotic Resistance ◽  
Intensive Care ◽  
Blood Culture ◽  
Bacterial Pathogens ◽  
Gram Negative ◽  
Specialized Hospital ◽  
Resistance Patterns ◽  
The University ◽  
Antibiotic Resistance Patterns

Abstract Abstract Background: The burden of bloodstream infection and antibiotic resistance in intensive care unit (ICU) is high when compared with other settings. The data on the changing antibiotic resistance trends are important for infection control activities. There is no sufficient data in the intensive care units of this hospital. Objective: The aims of this study were to assess the magnitude and risk factors of bacterial pathogens and their antibiotic resistance patterns of blood culture isolates from ICU patients at the University of Gondar Comprehensive Specialized Hospital, Gondar, Ethiopia. Materials and Methods: A cross-sectional study was conducted from February to May 2018.Blood specimen were collected from 384 patients and inoculated on appropriate culture media. Identification of bacterial pathogens and antibiotic susceptibility tests were performed using bacteriological standard methods. Presence of Extended Spectrum Beta Lactamase (ESBL) enzymes was confirmed by combined disk diffusion method. Data were analyzed using SPSS version 20. Result: Of the total 384 study participants, 96(25%) were culture positive. Majority of bacteria isolates 67(69.8%) were Gram negative. The commonly isolated bacterial species were K.pneumoniae 18(18.8%), Coagulase negative Staphylococcus 13(13.5%), K.ozanae 10(10.4%), K.rhinose 8(8.3%) and E.coli, E.cloacae, Citrobacter species, S.aureus each accounts 7(7.3%). Gram negative isolates were found to be resistant to ampicillin 66(98%), amoxicillin/clavulanate 64(95%) and ceftriaxone 52(77.6%). However, amikacin 64(95.5%), meropenem 58(87%) and Ciprofloxacin 56(83.6%) were relatively effective drugs. Gram positive isolates were found to be resistant to Penicillin 28(96.5%), amoxicillin/clavulanate27 (93.1%) and erythromycin 26(90%). They were sensitive to ciprofloxacin 22(79%) and clindamycin 24(83%). Methicillin resistant S.aureus accounted 4(57.1%) and ESBL enzyme producing Gram negative isolates accounted 41(78.8%). Conclusion: Klebsiella species were the predominant bacterial isolates in ICU settings. Antibiotic resistance due to ESBL enzyme production is alarmingly high. This result might be a reflection of inappropriate use of antibiotics and poor infection prevention control practice in these settings. Key words: Antibiotic resistance, ICU, ESBL, Gondar Ethiopia.

scholarly journals Pattern of Bacterial Pathogens and Their Susceptibility Isolated from Surgical Site Infections at Selected Referral Hospitals, Addis Ababa, Ethiopia

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Walelign Dessie ◽  
Gebru Mulugeta ◽  
Surafael Fentaw ◽  
Amete Mihret ◽  
Mulu Hassen ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Culture Media ◽  
Addis Ababa ◽  
Bacterial Pathogens ◽  
Surgical Site Infections ◽  
Multidrug Resistant ◽  
Cross Sectional ◽  
Gram Negative ◽  
E Coli ◽  
Medical College

Background. The emergence of multidrug resistant bacterial pathogens in hospitals is becoming a challenge for surgeons to treat hospital acquired infections.Objective. To determine bacterial pathogens and drug susceptibility isolated from surgical site infections at St. Paul Specialized Hospital Millennium Medical College and Yekatit 12 Referral Hospital Medical College, Addis Ababa, Ethiopia.Methods. A cross-sectional study was conducted between October 2013 and March 2014 on 107 surgical site infected patients. Wound specimens were collected using sterile cotton swab and processed as per standard operative procedures in appropriate culture media; and susceptibility testing was done using Kirby-Bauer disc diffusion technique. The data were analyzed by using SPSS version 20.Result. From a total of 107 swabs collected, 90 (84.1%) were culture positive and 104 organisms were isolated.E. coli(24 (23.1%)) was the most common organism isolated followed by multidrug resistantAcinetobacterspecies (23 (22.1%)). More than 58 (75%) of the Gram negative isolates showed multiple antibiotic resistance (resistance ≥ 5 drugs). Pan-antibiotic resistance was noted among 8 (34.8%)Acinetobacterspecies and 3 (12.5%)E. coli. This calls for abstinence from antibiotic abuse.Conclusion. Gram negative bacteria were the most important isolates accounting for 76 (73.1%). Ampicillin, amoxicillin, penicillin, cephazoline, and tetracycline showed resistance while gentamicin and ciprofloxacin were relatively effective antimicrobials.

scholarly journals Clinical profile, bacterial profile and outcomes of acute bacterial meningitis in a tertiary care hospital– one year study

2017 ◽  
Vol 4 (2) ◽  
pp. 502
Author(s):  
Ajay Kumar Sarvepalli ◽  
Prakash Kalakappa Dharana
Keyword(s):  
Developing Countries ◽  
Antibiotic Resistance ◽  
Bacterial Meningitis ◽  
Bacterial Pathogens ◽  
Clinical Profile ◽  
Acute Bacterial Meningitis ◽  
Care Hospital ◽  
Gram Positive ◽  
Gram Negative ◽  
One Year

Background: Bacterial meningitis is still one of the major causes of mortality and morbidity among all groups in developing countries. The mortality and prevalence of common pathogens has reduced in developing countries with implementation of successful vaccination against the pathogens. Laboratory surveillance of pathogens is crucial in formulating the empirical treatment guidelines and to identify the targets of immunization. The present study was undertaken to evaluate the clinical profile, bacterial pathogens and their antibiotic sensitivity pattern of the pathogens.  The outcome of the cases was recorded and followed for six months to detect any neurological sequelae.Methods: A one year prospective cross sectional study was done and all suspected cases of acute bacterial meningitis (ABM) were screened and confirmed by diagnostic criteria. Clinical features were recorded and entered into the case sheet. CSF culture was done and biochemical analysis and cell counts were performed. All the data was entered in Microsoft excel and analysed.Results: A total of 547 cases were screened and 282 confirmed with 164 males and 116 females. 282 pathogens were isolated with 266 bacterial and 12 fungal isolates. Gram negative bacterial pathogens were predominant than gram positive. Streptococcus pneumoniae was the common isolate in the study followed by others like S. aureus, Coagulase negative staphylococci and Acinetobacter sp., Escherichia coli, Klebsiella pneumoniae and meningococci. Candida albicans and Cryptococcus sp. were fungal pathogens. Community acquired meningitis was commonest cause and seen in 51-60 years of age. Gram positive pathogens exhibited maximum sensitivity to vancomycin and linezolid whereas Gram negative pathogens to carbapenems.Conclusions: There is an overwhelming need to formulate policies in the management of cases of ABM. The rationale use of antibiotics is necessary to prevent the development of antibiotic resistance. Hence minimizing the emergence of antibiotic resistance and its spread is necessary, which can be achieved by regular prevalence and antibiotic susceptibility studies.

scholarly journals Adjunctive transferrin to reduce the emergence of antibiotic resistance in Gram-negative bacteria

2019 ◽  
Vol 74 (9) ◽  
pp. 2631-2639 ◽  
Author(s):  
Brian M Luna ◽  
Ksenia Ershova ◽  
Jun Yan ◽  
Amber Ulhaq ◽  
Travis B Nielsen ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Pathogens ◽  
Microbial Pathogens ◽  
Gram Negative Bacteria ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Resistant Mutants ◽  
Time Kill ◽  
Emergence Of Resistance

AbstractBackgroundNew strategies are needed to slow the emergence of antibiotic resistance among bacterial pathogens. In particular, society is experiencing a crisis of antibiotic-resistant infections caused by Gram-negative bacterial pathogens and novel therapeutics are desperately needed to combat such diseases. Acquisition of iron from the host is a nearly universal requirement for microbial pathogens—including Gram-negative bacteria—to cause infection. We have previously reported that apo-transferrin (lacking iron) can inhibit the growth of Staphylococcus aureus in culture and diminish emergence of resistance to rifampicin.ObjectivesTo define the potential of apo-transferrin to inhibit in vitro growth of Klebsiella pneumoniae and Acinetobacter baumannii, key Gram-negative pathogens, and to reduce emergence of resistance to antibiotics.MethodsThe efficacy of apo-transferrin alone or in combination with meropenem or ciprofloxacin against K. pneumoniae and A. baumannii clinical isolates was tested by MIC assay, time–kill assay and assays for the selection of resistant mutants.ResultsWe confirmed that apo-transferrin had detectable MICs for all strains tested of both pathogens. Apo-transferrin mediated an additive antimicrobial effect for both antibiotics against multiple strains in time–kill assays. Finally, adding apo-transferrin to ciprofloxacin or meropenem reduced the emergence of resistant mutants during 20 day serial passaging of both species.ConclusionsThese results suggest that apo-transferrin may have promise to suppress the emergence of antibiotic-resistant mutants when treating infections caused by Gram-negative bacteria.

The Characterization of Antibiotic Resistance of Bacterial Isolates from Intensive Care Unit Patient Samples in a University Affiliated Hospital in Romania

2019 ◽  
Vol 70 (5) ◽  
pp. 1778-1783
Author(s):  
Andreea-Loredana Golli ◽  
Floarea Mimi Nitu ◽  
Maria Balasoiu ◽  
Marina Alina Lungu ◽  
Cristiana Cerasella Dragomirescu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Bacterial Pathogens ◽  
Resistance Rate ◽  
Resistance Pattern ◽  
Bacterial Isolates ◽  
E Coli ◽  
Acinetobacter Spp ◽  
Almost All ◽  
Klebsiella Spp

To determine the resistance pattern of bacterial pathogens involved in infections of the patients aged between 18-64 years, admitted in a ICU from a 1518-bed university-affiliated hospital. A retrospective study of bacterial pathogens was carried out on 351 patients aged between 18-64 years admitted to the ICU, from January to December 2017. In this study there were analysed 469 samples from 351 patients (18-64 years). A total of 566 bacterial isolates were obtained, of which 120 strains of Klebsiella spp. (35.39%%), followed by Nonfermenting Gram negative bacilli, other than Pseudomonas and Acinetobacter (NFB) (75- 22.12%), Acinetobacter spp. (53 - 15.63%), Pseudomonas aeruginosa and Proteus (51 - 15.04%), and Escherichia coli (49 - 14.45%). The most common isolates were from respiratory tract (394 isolates � 69.61%). High rates of MDR were found for Pseudomonas aeruginosa (64.70%), MRSA (62.65%) and Klebsiella spp. (53.33%), while almost all of the isolated NFB strains were MDR (97.33%). There was statistic difference between the drug resistance rate of Klebsiella and E. coli strains to ceftazidime and ceftriaxone (p[0.001), cefuroxime (p[0.01) and to cefepime (p[0.01). The study revealed an alarming pattern of antibiotic resistance in the majority of ICU isolates.

Extended Spectrum Beta Lactamase (ESBL), bla TEM,bla SHVand bla CTX-M,resistance genes in Community and Healthcare Associated Gram Negative Bacteria from Osun State, Nigeria

2020 ◽  
Vol 20 ◽  
Author(s):  
Ganiyat Shitta ◽  
Olufunmilola Makanjuola ◽  
Olusolabomi Adefioye ◽  
Olugbenga Adekunle Olowe
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Gram Negative Bacteria ◽  
Beta Lactamase ◽  
Multiple Antibiotic Resistance ◽  
Esbl Production ◽  
Gram Negative ◽  
Extended Spectrum Beta Lactamase ◽  
Healthcare Associated ◽  
Esbl Producers

Background: Extended Spectrum Beta Lactamase (ESBL) production in gram negative bacteria confers multiple antibiotic resistance, adversely affecting antimicrobial therapy in infected individuals. ESBLs result from mutations in β-lactamases encoded mainly by the bla TEM,bla SHVand bla CTX-Mgenes. The prevalence of ESBL producing bacteria has been on the increase globally especially its upsurge among isolates from community-acquired infections. Aim: To determine ESBL prevalence and identify ESBL genes among clinical isolates in Osun State, Nigeria. Material and Methods: A cross-sectional study was carried out from August 2016 –July 2017 in Osun State, Nigeria. Three hundred and sixty Gram negative bacteria recovered from clinical samples obtained from both community and healthcare associated infections were tested. They included147 Escherichia coli(40.8%), 116 Klebsiella spp(32.2%), 44 Pseudomo-nas aeruginosa(12.2%) and23 Proteus vulgaris (6.4%) isolates. Others were Acinetobacter baumannii, Serratia rubidae, Citrobacter spp, Enterobacter spp and Salmonella typhi. Disk diffusion antibiotic susceptibility testing was carried out, isolates were screened for ESBL production and confirmed using standard laboratory procedures. ESBLs resistance genes were identified by Polymerase Chain Reaction (PCR). Results: All isolates demonstrated multiple antibiotic resistance. Resistance to ampicillin, amoxicillin with clavulanate and erythromycin was 100%, whereas resistance to Imipenem was very low (5.0%). : Overall prevalence of ESBL producers was 41.4% with Klebsiellaspp as the highest ESBL producing Enterobacteriacaea. ESBL producers were more prevalent among the hospital pathogens than community pathogens, 58% vs 29.5% (p=0.003). ESBL genes were detected in all ESBL producers with the blaCTX-Mgene predominating (47.0%) followed by blaTEM(30.9%) and blaSHVgene was the least, 22.1%. The blaCTX-Mgene was also the most prevalent in the healthcare pathogens (62%) but it accounted for only 25% in those of community origin. Conclusion: A high prevalence of ESBL producing gram negative organisms occurs both in healthcare and in the community in our environment with the CTX-M variant predominating. Efforts to control spread of these pathogens should be addressed.

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