scholarly journals Gene-gene interactions dictate ciprofloxacin resistance in Pseudomonas aeruginosa and facilitate prediction of resistance phenotype from genome sequence data

2021 ◽  
Author(s):  
Attika Rehman ◽  
Julie Jeukens ◽  
Roger C Levesque ◽  
Iain L Lamont
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Inhibitory Concentration ◽  
Sequence Data ◽  
Gene Interactions ◽  
Genome Sequences ◽  
Strain Pao1 ◽  
Resistance Phenotype ◽  
Ciprofloxacin Resistance ◽  
Susceptibility Profiles

Ciprofloxacin is one of the most widely used antibiotics for treating Pseudomonas aeruginosa infections. However P. aeruginosa acquires mutations that confer ciprofloxacin resistance, making treatment more difficult. Resistance is multifactorial, with mutations in multiple genes influencing the resistance phenotype. However the contributions of individual mutations and mutation combinations to the amounts of ciprofloxacin that P. aeruginosa can tolerate are not well understood. Engineering P. aeruginosa strain PAO1 to contain mutations in any one of the resistance-associated genes gyrA, nfxB, rnfC, parC and parE showed that only gyrA mutations increased the Minimum Inhibitory Concentration (MIC) for ciprofloxacin. Mutations in parC and parE increased the MIC of a gyrA mutant, making the bacteria ciprofloxacin resistant. Mutations in nfxB and rnfC increased the MIC, conferring resistance, only if both were mutated in a gyrA background. Mutations in all of gyrA, nfxB, rnfC and parC/E further increased the MIC. These findings reveal an epistatic network of gene-gene interactions in ciprofloxacin resistance. We used this information to predict ciprofloxacin resistance/susceptibility for 274 isolates of P. aeruginosa from their genome sequences. Antibiotic susceptibility profiles were predicted correctly for 84% of the isolates. The majority of isolates for which prediction was unsuccessful were ciprofloxacin resistant, demonstrating the involvement of additional as yet unidentified genes and mutations in resistance. Our data show that gene-gene interactions can play an important role in antibiotic resistance and can be successfully incorporated into models predicting resistance phenotype.

scholarly journals Mechanisms for Development of Ciprofloxacin Resistance in a Clinical Isolate of Pseudomonas aeruginosa

2021 ◽  
Vol 11 ◽  
Author(s):  
Congjuan Xu ◽  
Huimin Liu ◽  
Xiaolei Pan ◽  
Zhenzhen Ma ◽  
Dan Wang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Clinical Isolate ◽  
Gene Editing ◽  
Molecular Mechanisms ◽  
Inhibitory Concentration ◽  
Fourfold Increase ◽  
Ciprofloxacin Resistance ◽  
First Time ◽  
Acquired Antibiotic Resistance

Treatment of infections by Pseudomonas aeruginosa is difficult due to its high intrinsic and acquired antibiotic resistance. Upon colonization in the human hosts, P. aeruginosa accumulates genetic mutations that confer the bacterium antibiotic resistance and ability to better live in the host environment. Characterizing the evolutionary traits would provide important insights into the development of effective combinatory antibiotic therapies to cure P. aeruginosa infections. In this work, we performed a detailed analysis of the molecular mechanisms by which a clinical isolate (CSP18) yields a ciprofloxacin-resistant derivative (CRP42). Genomic DNA re-sequencing and RNAseq were carried out to compare the genomic mutational signature and transcriptional profiles between the two isolates. The results indicated that D87G mutation in GyrA, together with MexEF-OprN hyper-expression caused by F7S mutation in MexS, was responsible for the increased resistance to ciprofloxacin in the isolate CRP42. Further simulation of CRP42 by gene editing in CSP18 demonstrated that D87G mutation in GyrA rendered CSP18 a fourfold increase in minimum inhibitory concentration against ciprofloxacin, while F7S mutation in MexS conferred an additional eightfold increase. Our experimental results demonstrate for the first time that the clinically relevant F7S point mutation in MexS results in hyper-expression of the mexEF-oprN and thus confers P. aeruginosa resistance to ciprofloxacin.

scholarly journals Draft Genome Sequences of Five Pseudomonas aeruginosa Clinical Strains Isolated from Sputum Samples from Cystic Fibrosis Patients: TABLE 1

2016 ◽  
Vol 4 (1) ◽  
Author(s):  
M. B. Couger ◽  
Anna Wright ◽  
Erika I. Lutter ◽  
Noha Youssef
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Virulence Factors ◽  
Resistance Genes ◽  
Draft Genome ◽  
Antibiotic Resistance Genes ◽  
Genome Sequences ◽  
Clinical Strains ◽  
Chronic Colonization

We report here the draft genome sequences of five Pseudomonas aeruginosa isolates obtained from sputum samples from two cystic fibrosis patients with chronic colonization. These closely related strains harbor 225 to 493 genes absent from the P. aeruginosa POA1 genome and contain 178 to 179 virulence factors and 29 to 31 antibiotic resistance genes.

scholarly journals Use of suppression subtractive hybridization to examine the accessory genome of the Liverpool cystic fibrosis epidemic strain of Pseudomonas aeruginosa

2006 ◽  
Vol 55 (6) ◽  
pp. 677-688 ◽  
Author(s):  
Catherine H. M. Smart ◽  
Martin J. Walshaw ◽  
C. Anthony Hart ◽  
Craig Winstanley
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Suppression Subtractive Hybridization ◽  
Sequence Data ◽  
Pcr Amplification ◽  
Subtractive Hybridization ◽  
Epidemic Strain ◽  
Strain Pao1 ◽  
The Uk ◽  
Specific Sequences

The Liverpool epidemic strain (LES) of Pseudomonas aeruginosa has been highly successful at colonizing cystic fibrosis (CF) patients throughout the UK, has replaced previously established strains in CF patients, has caused infections of non-CF parents of CF patients, and can cause greater morbidity in CF than other strains of P. aeruginosa. Using suppression subtractive hybridization (SSH) to identify strain-specific sequences, a diagnostic test for the LES based on PCR amplification of SSH sequence PS21 had previously been developed. In this study, the SSH sequence database of LES was substantially increased, using both extension of previous sequences and new rounds of subtraction. Of 92 SSH sequences identified as present in the LES but absent from strain PAO1, 25 were assessed for prevalence amongst a strain panel consisting mainly of LES and non-LES CF isolates. Preliminary analysis of genome sequence data indicated that all SSH sequences that were LES specific or found only rarely in other strains of P. aeruginosa were present on one of three contigs. All of the SSH sequences screened were either unstable amongst LES isolates or were not completely LES specific. Rare false positives were found with the PS21 test. The authors suggest that a second PCR assay designed to detect SSH sequence LESF9 can be used to confirm the identity of the most prevalent CF epidemic lineage in the UK.

scholarly journals Comprehensive analysis of imipenemase (IMP)-type metallo-Beta-lactamase showing global distribution threating Asia

2022 ◽  
Author(s):  
Pisut Pongchaikul ◽  
Paninee Mongkolsuk
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Antimicrobial Resistance ◽  
Comprehensive Analysis ◽  
Regional Level ◽  
Global Distribution ◽  
Beta Lactamase ◽  
Global Level ◽  
Beta Lactam ◽  
Susceptibility Profiles

Antibiotic resistance, particularly beta-lactam resistance, is a major problem worldwide. Imipenemase or IMP-type metallo-beta-lactamase (MBL) has become a more prominent enzyme, especially in Asia, since it was discovered in the 1990s in Japan. There are currently more than 91 variants of IMP-type enzymes. The most commonly identified variant of IMP-type enzymes is IMP-1 variant. IMP-type MBLs have been identified in more than 10 species in Enterobacterales. Pseudomonas aeruginosa is the most frequent carrier of IMP-type enzymes worldwide. In Asia, IMP-type MBLs have been distributed in many countries in the region. This work investigated a variety of currently available IMP-type MBLs in both global level and regional level. Out of 88 variants of IMP-type MBLs reported worldwide, only 32 variants were found to have susceptibility profiles. Most of the IMP-type MBLs were resistant to Carbapenems, especially Imipenem and Meropenem, followed by the 3rd generation cephalosporins, and interestingly, monobactams. Our results comprehensively indicated the distribution of IMP-type MBLs in Asia and raised the awareness of the situation of antimicrobial resistance in the region.

Pharmacodynamic Modeling of Risk Factors for Ciprofloxacin Resistance in Pseudomonas aeruginosa

2000 ◽  
Vol 21 (S1) ◽  
pp. S9-S11 ◽  
Author(s):  
Judith M. Hyatt ◽  
Jerome J. Schentag
Keyword(s):  
Risk Factors ◽  
Pseudomonas Aeruginosa ◽  
Length Of Stay ◽  
Respiratory Tract ◽  
Inhibitory Concentration ◽  
Concentration Curve ◽  
Pharmacodynamic Modeling ◽  
Ciprofloxacin Resistance ◽  
Group 2 ◽  
Dichotomous Variables

AbstractObjective:To determine risk factors for ciprofloxacin resistance in Pseudomonas aeruginosa.Methods:Patients with cultures (any site) positive for P aeruginosa, susceptible to ciprofloxacin, between January 1993 and December 1996 were identified using a computerized database. Factors predictive of emergence of ciprofloxacin resistance in P aeruginosa strains isolated from the same cultured site, within 21 days of the initial culture, were determined. Factors considered included length of stay prior to initial P aeruginosa culture, isolation site, initial minimum inhibitory concentration (MIC), antibiotic area under the 24-hour concentration curve (AUC24), total area under the 24-hour inhibitory concentration curve ([AUIC24] AUC24/MIC summed for all active drugs), antibiotic(s) used as dichotomous variables (yes/no), and use of monotherapy or combination therapy.Results:Of 635 patients, 43 (7%) subsequently had ciprofloxacin-resistant P aeruginosa isolated. Four significantly differing patient groups were identified: group 1, P aeruginosa isolates from all sites other than the respiratory tract, treated with any drugs; group 2, respiratory tract isolates treated with drugs other than ciprofloxacin; group 3, respiratory tract isolates treated with ciprofloxacin at AUIC24 > 110 (μg·h/mL)/μg/mL; and group 4, respiratory tract isolates treated with ciprofloxacin at AUIC24 ≤110 (μg·h/mL)/μg/mL. The observed percentage resistant was a continuous function of prior length of stay in all four groups. Respiratory tract isolates had higher rates of ciprofloxacin resistance (12%) than isolates from other infection sites (4%). Respiratory tract isolates exposed to ciprofloxacin at AUIC24 ≤110 (μg·h/mL)/μg/mL had the highest resistance (17%). At AUIC24 >110 (μg·h/mL)/μg/mL, resistance was decreased to 11%, a rate similar to that seen in respiratory isolates not exposed to ciprofloxacin (7%).Conclusions:Application of pharmacokinetic and pharmacodynamic principles to dosing of ciprofloxacin may reduce the risk of ciprofloxacin resistance to the level seen in isolates exposed to other agents.

scholarly journals Draft Genome Sequences of Cefepime-Resistant and -Susceptible Escherichia coli Strains and Imipenem-Resistant and -Susceptible Pseudomonas aeruginosa Strains

2021 ◽  
Vol 10 (48) ◽  
Author(s):  
Kendra Batchelder ◽  
Liz Ward ◽  
Elsa Collins ◽  
Caitlin Miles ◽  
Stefania Palm ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Draft Genome ◽  
Antibiotic Resistance Genes ◽  
Genome Sequences ◽  
Content Type ◽  
E Coli

Draft genome sequences of Escherichia coli and Pseudomonas aeruginosa strains collected from clinical infections were used to determine the prevalence of newly emerging antibiotic resistance genes in Maine. Comparisons between cefepime-resistant and -susceptible E. coli strains and imipenem-resistant and -susceptible P. aeruginosa strains are being conducted.

scholarly journals Draft Genome Sequences of 40 Pseudomonas aeruginosa Clinical Strains Isolated from the Sputum of a Single Cystic Fibrosis Patient Over an 8-Year Period

2016 ◽  
Vol 4 (6) ◽  
Author(s):  
Irene Bianconi ◽  
Silvia D’Arcangelo ◽  
Mattia Benedet ◽  
Kate E. Bailey ◽  
Alfonso Esposito ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Population Structure ◽  
Cystic Fibrosis Patient ◽  
Draft Genome ◽  
Multidrug Resistant ◽  
Genome Sequences ◽  
Clinical Strains

We report draft genome sequences of 40 Pseudomonas aeruginosa strains, isolated from the sputum of a single cystic fibrosis patient over eight years. Analyses indicated a correlation between multidrug-resistant phenotypes and population structure. Our data provide new insights into the mechanisms leading to acquisition of antibiotic resistance in P. aeruginosa .

scholarly journals Effects of Glycyrrhizin on Multi-Drug Resistant Pseudomonas aeruginosa

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 766
Author(s):  
Nicholas J. Carruthers ◽  
Sharon A. McClellan ◽  
Mallika Somayajulu ◽  
Ahalya Pitchaikannu ◽  
Denise Bessert ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Type Iii Secretion ◽  
Biofilm Formation ◽  
Inhibitory Concentration ◽  
Drug Resistant ◽  
Liquid Chromatography Mass Spectrometry ◽  
Corneal Epithelial ◽  
Type Iii ◽  
Biofilm Dispersal

The effects of glycyrrhizin (GLY) on multi-drug resistant (MDR) systemic (MDR9) vs. ocular (B1045) Pseudomonas aeruginosa clinical isolates were determined. Proteomes of each isolate with/without GLY treatment were profiled using liquid chromatography mass spectrometry (LC-MS/MS). The effect of GLY on adherence of MDR isolates to immortalized human (HCET) and mouse (MCEC) corneal epithelial cells, and biofilm and dispersal was tested. Both isolates were treated with GLY (0.25 minimum inhibitory concentration (MIC), 10 mg/mL for MDR9 and 3.75 mg/mL for B1045) and subjected to proteomic analysis. MDR9 had a greater response to GLY (51% of identified proteins affected vs. <1% in B1045). In MDR9 vs. controls, GLY decreased the abundance of proteins for: antibiotic resistance, biofilm formation, and type III secretion. Further, antibiotic resistance and type III secretion proteins had higher control abundances in MDR9 vs. B1045. GLY (5 and 10 mg/mL) significantly reduced binding of both isolates to MCEC, and B1045 to HCET. MDR9 binding to HCET was only reduced at 10 mg/mL GLY. GLY (5 and 10 mg/mL) enhanced dispersal for both isolates, at early (6.5 h) but not later times (24–72 h). This study provides evidence that GLY has a greater effect on the proteome of MDR9 vs. B1045, yet it was equally effective at disrupting adherence and early biofilm dispersal.

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