The Role of Fluoroquinolones in the Promotion of Alginate Synthesis and Antibiotic Resistance in Pseudomonas aeruginosa

1997 ◽  
Vol 35 (2) ◽  
pp. 103-108 ◽  
Author(s):  
Sophia E. Piña ◽  
Stephen J. Mattingly
2009 ◽  
Vol 53 (6) ◽  
pp. 2483-2491 ◽  
Author(s):  
L. F. Mandsberg ◽  
O. Ciofu ◽  
N. Kirkby ◽  
L. E. Christiansen ◽  
H. E. Poulsen ◽  
...  

ABSTRACT The chronic Pseudomonas aeruginosa infection of the lungs of cystic fibrosis (CF) patients is characterized by the biofilm mode of growth and chronic inflammation dominated by polymorphonuclear leukocytes (PMNs). A high percentage of P. aeruginosa strains show high frequencies of mutations (hypermutators [HP]). P. aeruginosa is exposed to oxygen radicals, both those generated by its own metabolism and especially those released by a large number of PMNs in response to the chronic CF lung infection. Our work therefore focused on the role of the DNA oxidative repair system in the development of HP and antibiotic resistance. We have constructed and characterized mutT, mutY, and mutM mutants in P. aeruginosa strain PAO1. The mutT and mutY mutants showed 28- and 7.5-fold increases in mutation frequencies, respectively, over that for PAO1. These mutators had more oxidative DNA damage (higher levels of 7,8-dihydro-8-oxodeoxyguanosine) than PAO1 after exposure to PMNs, and they developed resistance to antibiotics more frequently. The mechanisms of resistance were increased β-lactamase production and overexpression of the MexCD-OprJ efflux-pump. Mutations in either the mutT or the mutY gene were found in resistant HP clinical isolates from patients with CF, and complementation with wild-type genes reverted the phenotype. In conclusion, oxidative stress might be involved in the development of resistance to antibiotics. We therefore suggest the possible use of antioxidants for CF patients to prevent the development of antibiotic resistance.


1982 ◽  
Vol 28 (2) ◽  
pp. 169-175 ◽  
Author(s):  
R. Allan Scudamore ◽  
Morris Goldner

The role of the outer membrane (OM) was investigated in relation to the high level of intrinsic antibiotic resistance of Pseudomonas aeruginosa ATCC 9027. OM penetration barriers were measured by comparing turbidimetric growth curves of EDTA-treated and normal cells exposed to carbenicillin, moxalactam (LY 127935), gentamicin, tobramycin, rifampin, novobiocin, and vancomycin. OM barriers were also measured for carbenicillin and moxalactam in P. aeruginosa strain K 799/61, a hypersusceptible mutant presumed to have lost its penetration barrier in the cell envelope. Most antibiotics penetrated the OM efficiently and there was little difference between the two strains. The evidence therefore suggests that intrinsic resistance of P. aeruginosa, especially to the beta-lactam antibiotics, is not mainly due to the OM. A penetration barrier situated deeper within the cell envelope is hypothesized, the size of which in relation to any antibiotic may be estimated by comparing the IC50 values of EDTA-treated cells of the two strains.


2014 ◽  
Vol 63 (4) ◽  
pp. 544-555 ◽  
Author(s):  
Hansi Kumari ◽  
Deepak Balasubramanian ◽  
Diansy Zincke ◽  
Kalai Mathee

Pseudomonas aeruginosa is one of the most dreaded opportunistic pathogens accounting for 10 % of hospital-acquired infections, with a 50 % mortality rate in chronically ill patients. The increased prevalence of drug-resistant isolates is a major cause of concern. Resistance in P. aeruginosa is mediated by various mechanisms, some of which are shared among different classes of antibiotics and which raise the possibility of cross-resistance. The goal of this study was to explore the effect of subinhibitory concentrations (SICs) of clinically relevant antibiotics and the role of a global antibiotic resistance and virulence regulator, AmpR, in developing cross-resistance. We investigated the induction of transient cross-resistance in P. aeruginosa PAO1 upon exposure to SICs of antibiotics. Pre-exposure to carbapenems, specifically imipenem, even at 3 ng ml−1, adversely affected the efficacy of clinically used penicillins and cephalosporins. The high β-lactam resistance was due to elevated expression of both ampC and ampR, encoding a chromosomal β-lactamase and its regulator, respectively. Differences in the susceptibility of ampR and ampC mutants suggested non-AmpC-mediated regulation of β-lactam resistance by AmpR. The increased susceptibility of P. aeruginosa in the absence of ampR to various antibiotics upon SIC exposure suggests that AmpR plays a major role in the cross-resistance. AmpR was shown previously to be involved in resistance to quinolones by regulating MexEF–OprN efflux pump. The data here further indicate the role of AmpR in cross-resistance between quinolones and aminoglycosides. This was confirmed using quantitative PCR, where expression of the mexEF efflux pump was further induced by ciprofloxacin and tobramycin, its substrate and a non-substrate, respectively, in the absence of ampR. The data presented here highlight the intricate cross-regulation of antibiotic resistance pathways at SICs of antibiotics and the need for careful assessment of the order of antibiotic regimens as this may have dire consequences. Targeting a global regulator such as AmpR that connects diverse pathways is a feasible therapeutic approach to combat P. aeruginosa pathogenesis.


2011 ◽  
Vol 56 (2) ◽  
pp. 1128-1132 ◽  
Author(s):  
Lucía Fernández ◽  
Elena B. M. Breidenstein ◽  
Diana Song ◽  
Robert E. W. Hancock

ABSTRACTPseudomonas aeruginosapossesses complex regulatory networks controlling virulence and survival under adverse conditions, including antibiotic pressure, which are interconnected and share common regulatory proteins. Here, we screen a panel of 13 mutants defective in intracellular proteases and demonstrate that, in addition to the known alterations in Lon and AsrA mutants, mutation of three protease-related proteins PfpI, ClpS, and ClpP differentially affected antibiotic resistance, swarming motility, and biofilm formation.


2016 ◽  
Vol 101 ◽  
pp. 126-135 ◽  
Author(s):  
Ying Liang ◽  
Zisheng Guo ◽  
Lang Gao ◽  
Qianqian Guo ◽  
Liyue Wang ◽  
...  

2018 ◽  
Vol 7 (2) ◽  
pp. 40-46
Author(s):  
Jillian Pia Raquid ◽  
John Carlo Prieto ◽  
Danica Mae Arciaga ◽  
Rica Hazel Corpuz ◽  
Shally Mae Llorente ◽  
...  

2019 ◽  
Vol 41 part 1 (2) ◽  
pp. 56-60 ◽  
Author(s):  
O. M. Besedin ◽  
S. O. Kosulnikov ◽  
L. M. Storubel ◽  
S. I. Karpenko ◽  
S. O. Tarnopolsky ◽  
...  

The role of Pseudomonas aeruginosa isolates among the pathogens of surgical infection in purulent-septic surgery department for 2018 is determined. Investigated the antibiotic resistance of Pseudomonas aeruginosa hospital strains and the most effective antibiotics were investigated. Poly resistant in wound material were almost half of the cultures of Pseudomonas aeruginosa (19 strains, 45,2%). Carbapenem resistant Pseudomonas aeruginosa was found to be 47,1%. Of the aminoglycoside group antibiotics, Tobramycin (82,1%) showed the best sensitivity, Amikacin was sensitive in half of the microorganisms tested (55,0%). The sensitivity of cephalosporins ranged from 23,1% (Cefoperazone) to 40,5% (Ceftazidime). Even the use of the Sulbactam protective molecule did not improve the situation: 37,5% (Cefoperazone/ Sulbactam). For fluoroquinolones (Ciprofloxacin) sensitive third part of bacteria only. Piperacillin with Tazobactam, Fosfomycin, and Colistin E showed a high anti-pseudomonad efficacy. The use of anti-diarrhea bacteriophage was ineffective. Keywords: hospital strains, antibiotic resistance, Pseudomonas aeruginosa.


1985 ◽  
Vol 6 (4) ◽  
pp. 165-168
Author(s):  
Sandra M. Norris

The escalating role of Pseudomonas aeruginosa as a nosocomial pathogen, the relatively high mortality rate associated with pseudomonal infections, the intrinsic antibiotic resistance of this versatile, ubiquitous organism, and the growing number of reports of multiple antibiotic resistance developing during therapy of Pseudomonas infections prompt a review of currently available penicillins with antipseudomonal activity. Ticarcillin, piperacillin, mezlocillin and azlocillin have upstaged carbenicillin, the first antipseudomonal, β-lactam agent clinically used, with other products “in the wings.”


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