Experimental pulmonary infection of mice by tracheal intubation of Pseudomonas aeruginosa: the use of antineoplastic agents to overcome natural resistance

1977 ◽  
Vol 23 (6) ◽  
pp. 823-826 ◽  
Author(s):  
Lawrence B. Schook ◽  
Lee Carrick Jr. ◽  
Richard S. Berk
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Tracheal Intubation ◽  
Cytosine Arabinoside ◽  
Antineoplastic Agents ◽  
Pulmonary Infection ◽  
Single Injection ◽  
Antineoplastic Drug ◽  
Natural Resistance ◽  
Bacterial Challenge ◽  
Vincristine Sulfate

Tracheal intubation of viable Pseudomonas aeruginosa ATCC 19660 into the lungs of mice had no significant effect on the animals even with administration of organisms as high as 5.0 × 109 CFU. Animals treated with a single injection of an antineoplastic drug were, however, susceptible to bacterial challenge into the lungs. LD50 values of 4.1 × 107, 4.8 × 107and 1.0 × 108 CFU were obtained when animals were simultaneously infected and treated with methotrexate, vincristine sulfate, or cytosine arabinoside, respectively.

scholarly journals EPS4.02 Porphyromonas, a candidate biomarker for detection of Pseudomonas aeruginosa pulmonary infection in cystic fibrosis

2018 ◽  
Vol 17 ◽  
pp. S43 ◽  
Author(s):  
C.-A. Guilloux ◽  
G. Marenne ◽  
S. Mondot ◽  
C. Lamoureux ◽  
L. Billard ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Pulmonary Infection

scholarly journals Assignment of the Substrate-Selective Subunits of the MexEF-OprN Multidrug Efflux Pump of Pseudomonas aeruginosa

2000 ◽  
Vol 44 (3) ◽  
pp. 658-664 ◽  
Author(s):  
Hideaki Maseda ◽  
Hiroshi Yoneyama ◽  
Taiji Nakae
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Susceptibility ◽  
Efflux Pump ◽  
Functional Unit ◽  
Natural Resistance ◽  
Substrate Selectivity ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump ◽  
Additional Resistance ◽  
Functionally Diverse

ABSTRACT Pseudomonas aeruginosa expresses a low level of the MexAB-OprM efflux pump and shows natural resistance to many structurally and functionally diverse antibiotics. The mutation that has been referred to previously as nfxC expresses an additional efflux pump, MexEF-OprN, exhibiting resistance to fluoroquinolones, imipenem, and chloramphenicol and hypersusceptibility to β-lactam antibiotics. To address the antibiotic specificity of the MexEF-OprN efflux pump, we introduced a plasmid carrying themexEF-oprN operon into P. aeruginosa lacking the mexAB-oprM operon. The transformants exhibited resistance to fluoroquinolones, trimethoprim, and chloramphenicol but, unlike most nfxC-type mutants, did not show β-lactam hypersusceptibility. The transformants exhibited additional resistance to tetracycline. In the next experiment, we analyzed the MexEF-OprN pump subunit(s) responsible for substrate selectivity by expressing MexE, MexF, OprN, and MexEF in strains lacking MexA, MexB, OprM, and MexAB, respectively. The MexEF-OprM/ΔMexAB transformants exhibited MexEF-OprN-type pump function that rendered the strains resistant to fluoroquinolones and chloramphenicol but did not change susceptibility to β-lactam antibiotics compared with the host strain. The MexAB-OprN/ΔOprM, MexAF-OprM/ΔMexB, and MexEB-OprM/ΔMexA mutants exhibited antibiotic susceptibility indistinguishable from that in the mutant lacking both types of efflux pumps. The results imply that the MexEF-OprM pump selects substrates by a MexEF functional unit. Interestingly, OprN did not link functionally with the MexAB complex, despite the fact that OprM interacted functionally with MexEF.

Increased Survival in Irradiated Animals Treated With Bacterial Endotoxins

1957 ◽  
Vol 191 (1) ◽  
pp. 124-130 ◽  
Author(s):  
Willie W. Smith ◽  
Ilo M. Alderman ◽  
Ruth E. Gillespie
Keyword(s):  
Beneficial Effect ◽  
Single Injection ◽  
Gram Negative Bacteria ◽  
Bacterial Challenge ◽  
Gram Negative ◽  
Bacterial Endotoxins ◽  
Pseudomonas Infection

A single injection of endotoxin derived from Gram negative bacteria caused an increased survival in lethally irradiated animals when given immediately after or 24 hours before irradiation. Mice responded better to the injection before irradiation and hamsters to the injection after irradiation. The effect was associated with a reduction in infection, very pronounced in the case of α-streptococcus or Proteus and still significant in the case of Pseudomonas infection. No beneficial effect was obtained when mice were given three endotoxin injections during 1 week or six injections during 2 weeks prior to irradiation. The beneficial effect is not necessarily associated with the granulocytosis which begins within a few hours after the endotoxin injection, or with the conditions under which nonirradiated animals show an increased resistance to bacterial challenge.

scholarly journals Involvement of an Active Efflux System in the Natural Resistance of Pseudomonas aeruginosa to Aminoglycosides

1999 ◽  
Vol 43 (11) ◽  
pp. 2624-2628 ◽  
Author(s):  
Julio Ramos Aires ◽  
Thilo Köhler ◽  
Hiroshi Nikaido ◽  
Patrick Plésiat
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Regulatory Gene ◽  
Natural Resistance ◽  
Insertion Mutagenesis ◽  
Detectable Effect ◽  
Efflux System ◽  
Intrinsic Resistance ◽  
Cloning And Sequencing ◽  
Active Efflux ◽  
Energy Dependent

ABSTRACT A mutant, named 11B, hypersusceptible to aminoglycosides, tetracycline, and erythromycin was isolated after Tn501insertion mutagenesis of Pseudomonas aeruginosa PAO1. Cloning and sequencing experiments showed that 11B was deficient in an, at that time, unknown active efflux system that contains homologs of MexAB. This locus also contained a putative regulatory gene,mexZ, transcribed divergently from the efflux operon. Introduction of a recombinant plasmid that carries the genes of the efflux system restored the resistance of 11B to parental levels, whereas overexpression of these genes strongly increased the MICs of substrate antibiotics for the PAO1 host. Antibiotic accumulation studies confirmed that this new system is an energy-dependent active efflux system that pumps out aminoglycosides. Furthermore, this system appeared to function with an outer membrane protein, OprM. While the present paper was being written and reviewed, genes with a sequence identical to our pump genes, mexXY of P. aeruginosa, have been reported to increase resistance to erythromycin, fluoroquinolones, and organic cations inEscherichia coli hosts, although efflux of aminoglycosides was not examined (Mine et al., Antimicrob. Agents Chemother. 43:415–417, 1999). Our study thus shows that the MexXY system plays an important role in the intrinsic resistance of P. aeruginosato aminoglycosides. Although overexpression of MexXY increased the level of resistance to fluoroquinolones, disruption of themexXY operon in P. aeruginosa had no detectable effect on susceptibility to these agents.

scholarly journals Successful ceftolozane/tazobactam treatment of chronic pulmonary infection with pan‐resistant Pseudomonas aeruginosa

2015 ◽  
Vol 2 (2) ◽  
Author(s):  
Reham Soliman ◽  
Sarah Lynch ◽  
Emma Meader ◽  
Rachel Pike ◽  
Jane F. Turton ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Pulmonary Infection
Sign in / Sign up

Export Citation Format

Share Document