Pseudomonas, resistance

Contact dermatitis due to arbekacin has been reported (122). The risk of sensitization by topically administered gentamicin seems to be smaller. Nevertheless, and in order to avoid resistance, topical use should be restricted to life-endangering thermal burns and to severe skin infections in which strains of Pseudomonas resistant to other antibiotics are involved. 

Martin, G. B., Williams, J G. K., and Tanksley, S. D. (1991) Rapid identification of markers linked to a pseudomonas resistance gene in tomato by using random primers and near isogenic lines. Proc. Natl. Acad. Sci. USA 88,2336-2340. 

Porin channels are impHcated in the transport of cephalosporins because ceds deficient in porins are much more impermeable than are ceds that are rich in porins. The porins appear to function as a molecular sieve, adowing molecules of relatively low molecular weight to gain access to the periplasmic space by passive diffusion. In enterobacteria, a clear correlation exists between porin quantity and cephalosporin resistance, suggesting that the outer membrane is the sole barrier to permeabdity. However, such a relationship is not clearly defined for Pseudomonas aeruginosa where additional barriers may be involved (139,144,146). 

Some polymyxins are sold for second-line systemic therapy. Polymyxin B sulfate and colistimethate sodium can be used for intravenous, intramuscular, or intrathecal administration, especially for Pseudomonas aerupinosa mP QXiosis, but also for most other gram-negative organisms, such as those resistant to first-line antibiotics. Nephrotoxicity and various neurotoxicities are common in parenteral, but not in topical, use. Resistance to polymyxins develops slowly, involves mutation and, at least in some bacteria, adaptation, a poorly understood type of resistance that is rapidly lost on transfer to a medium free of polymyxin. Resistance can involve changes in the proteins, the lipopolysaccharides, and lipids of the outer membrane of the cell (52). Polymyxin and colistin show complete cross-resistance. 

The combined intrinsic activities of different efflux pumps play a major role for the intrinsic resistance of Gram-negative bacteria to macrolides and oxazolidi-nones as well as to the intrinsic resistance of Pseudomonas aeruginosa against a broad range of disinfectants and antibiotics. 

Nucleotidylation - the addition of adenylate-residues by Lnu enzymes - can also be the cause of resistance to lincosamide antibiotics in staphylococci and enterococci. A plasmid encoded ADP-ribosylating transferase (Arr-2) that leads to rifampicin resistance has been detected in various Enterobacteriaceae as well as in Pseudomonas aeruginosa. 

The next problem for H. Umezawa was to use his findings to design new kanamycin derivatives effective against resistant bacteria. The synthetic work was undertaken in cooperation with his brother. Prof Sumio Umezawa of Keio University, and one of the writers (T. Tsuchiya). The first useful derivatives active against resistant bacteria, namely, 3, 4 -dideoxy-kanamycin B (dibekacin) and 3 -deoxykanamycin A, were prepared in 1971. These were also found active against Pseudomonas known to have intrinsic resistance. These results supported the truth of H. Umezawa s theory. In the synthesis of dibekacin, the Tipson-Cohen method for introducing unsaturation, developed by one of the writers (D. Horton, 1966) for pyranoside... 

Dideoxykanamycin B active against kanamycin-resistant Escherichia coli and Pseudomonas aeruginosa," H. Umezawa, S. Umezawa, T. Tsuchiya, and Y. Okazaki, J. Antibiol., 24 (1971) 485-487. 

Pseudomonas aeruginosa is resistant to many antibacterial agents (Chapters 9,13) and is biochemically very versatile, being able to use many disinfectants as food sources. 

The mechanism of acquired resistance in Pseudomonas aeruginosa is different. Chromosomal mutations result in the increase of a specific outer membrane protein with a concomitant reduction in divalent cations. Polymyxins bind to the outer membrane at sites normally occupied by divalent cations, and therefore it is thought that a reduction in these sites will lead to decreased binding of the antibiotic with a consequent decreased susceptibility of the cell. 

Burkholderia (formeriy Pseudomonas) cepacia is intrinsically resistant to a number of biocides, notably benzalkonium chloride and chlorhexidine. Again, the outer membrane is likely to act as a permeability barrier. By contrasL Ps. stutzeri (an organism implicated in eye infections caused by some cosmetic products) is invariably intrinsically sensitive to a range of biocides, including QACs and chlorhexidine. This organism contains less wall muramic acid than other pseudomonads but it is imclear as to whether this could be a contributory factor in its enhanced biocide susceptibility. 

The degradation of phenylmercuric acetate to benzene, methylmercuric chloride to methane, and ethylmercuric chloride to ethane and Hg + is apparently carried out by different enzymes from the plasmid-carrying Escherichia coli strain K12 (R831) (Schottel 1978) and Pseudomonas sp. Resistance to organic mercury compounds has also been found in clinical isolates of nontuber-culous, rapidly growing mycobacteria (Steingrube et al. 1991) and can present a challenge in the clinical environment. 

Although reduction of chromate Cr to Cr has been observed in a number of bacteria, these are not necessarily associated with chromate resistance. For example, reduction of chromate has been observed with cytochrome Cj in Desulfovibrio vulgaris (Lovley and Phillips 1994), soluble chromate reductase has been purified from Pseudomonas putida (Park et al. 2000), and a membrane-bound reductase has been purified from Enterobacter cloacae (Wang et al. 1990). The flavoprotein reductases from Pseudomonas putida (ChrR) and Escherichia coli (YieF) have been purified and can reduce Cr(VI) to Cr(III) (Ackerley et al. 2004). Whereas ChrR generated a semi-quinone and reactive oxygen species, YieR yielded no semiquinone, and is apparently an obligate four-electron reductant. It could therefore present a suitable enzyme for bioremediation. 

Alvarez AH, R Moreno-Sanchez, C Cervantes (1999) Chromate efflux by means of the ChrA chromate resistance protein from Pseudomonas aeruginosa. J Bacterial 181 7398-7400. 

Junker F, JL Ramos (1999) Involvement of the cis/trans isomerase Cti in solvent resistance of Pseudomonas putida DOT-TIE. J Bacterial 181 5693-5700. 

Wilkinson SG (1968) Studies on the cell walls of pseudomonas species resistant to ethylenediaminetetra-ace-tic acid. J Gen Microbiol 54 195-213. 

Nagasawa T, H Ohkishi, B Kawakami, H Yamano, H Hosono, Y Tani, H Yamada (1982) 3-chloro-D-ala-nine chloride-lyase (deaminating) of Pseudomonas putida CR 1-1. Purification and characterization of a novel enzyme occurring in 3-chloro-D-alanine-resistant pseudomonads. J Biol Chem 257 13749-13756. 

Utsumi R et al. (1991) Molecular cloning and characterization of the fusaric acid-resistance gene from Pseudomonas cepacia. Agric Biol Chem 55 1913-1918. 

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