Pseudomonas antibiotic

The sulfated compounds MM 13902 (3, n = (5) and MM 17880 (4) are also broad-spectmm agents, but not as potent as thienamycia and all lack any significant activity against Pseudomonas (73). Many carbapenems are excellent inhibitors of isolated P-lactamases, particularly the olivanic acid sulfoxide MM 4550 (3, n = 1) (3). The possible mechanism of action of the carbapenems as inhibitors of P-lactamases has been discussed in some detail (74). Other carbapenems such as PS-5 (5) (75), the carpetimycins (76), asparenomycins (77), and pluracidomycins (8) are all highly active as antibiotics or P-lactamase inhibitors. The parent nucleus itself (1, X = CH2) is intrinsically active, but chemically unstable (9). 

Fosfadecin (186) and fosfocytocin (187) are adenine and cytosine nucleotide antibiotics isolated from the culture filtrates of Pseudomonas viridiflava PK-5 and P. fluorescens PK-52, respectively (283). Hydrolysis produces fosfoxacin which is also isolated from the culture filtrates. Compounds (186) and (187) inhibit gram-positive and gram-negative bacteria. 

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. 

Cefpiramide (64) is a third generation cephalosporin with a l-methyl-[lH)-tetra2ol-5-ylthio-methyl moiety at C-3 and an acylated -hydroxyphenylglycine moiety at C-7. It includes in its activity spectrum reasonable potency in vitro against many strains of Pseudomonas. It can be synthesized in a variety of ways including condensation of cephalosporin antibiotic 63 with 6-methyl-4-(l-H)-pyridone-3-carboxylic acid in the form of its active N-hydroxysuccinimide ester (62) to produce cefpiramide (64) [20,21],... 

Fosfomycin is an antibiotic produced by several Streptomyces species [95, 96] as well as by the Gram-negative Pseudomonas syringiae and Pseudomonas viridiflava. dl, 98] As an analogue of phosphoenolpyruvate, it irreversibly inhibits UDP-N-acetylglu-cosamine-3-O-enolpymvyltransferase (MurA), the enzyme that catalyzes the first step in peptidoglycan biosynthesis [99]. 

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. 

In Gram-negative bacteria, diffusion of (3-lactam antibiotics into the periplasm (where the activity of PBPs takes place) occurs via the channels that porins create in the outer membrane. The number and properties of the porin molecules are such that diffusion is relatively rapid in E. coli but much slower in Enterobacter and Pseudomonas. Mutants can be selected after the permeability of porin channels or their number has been decreased. A slow diffusion into... 

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 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. 

Schouten A, G van den Berg, C Edel-Hermann, C Steinberg, N Gautheron, C Alabouvette, CH de Vos, P Lemanceau, JM Raaijmakers (2004) Defense responses of Fusarium oxysporum to 2,4-diacetylphlo-roglucinol, a broad-spectrum antibiotic produced by Pseudomonas fluorescens. Mol Plant-Microbe Interact 17 1201-1211. 

Brodhagen M, MD Henkels, JE Loper (2004) Positive antoregnlation and signaling properties of pyolnteorin, an antibiotic produced by the biological control organism Pseudomonas fluorescens Pf-5. Appl Environ Microbiol 70 1758-1766. 

L. A. Harrison, L. Lctendre, P. Kovacevich, E. Pierson, and D. Weller, Purilication of an antibiotic effective against Gaeumannomyces graininis var. tritici produced by a biocontrol agetU, Pseudomonas aureofaciens. Soil Biology and Biochemistry 2.5 215 (1993). 

L. S. Thoma.show and D. M. Weller, Role of phenazine antibiotic from Pseudomonas fluorescens in biological control of Gaeumannomyces graminis var. tritici. Journal of Bacteriology 770 3499 (1988). 

C. R. Howell and R. D. Stipanovic, Control of Rhizoctonia solani on cotton seedlings with Pseudomonas fluorescens and with an antibiotic produced by the bacterium, Phytopathology 69 480 (1979). 

Antibiotic substances and their molecular genetics are summarized for the best studied system of fluorescent Pseudomonas, producing up to. seven different compounds. Similar extensive studies should be done for other important rhizosphere bacteria as potential important antagonists for root pathogens. The best-studied example for the effects of vitamins in the rhizosphere is biotin. The molecular genetics of production and uptake of vitamins in the plant-microbe interaction is also a field of interesting future work. 

M. G. Bangera and L. S. Thomashow, Characterization of a genomic locus required for synthesis of the antibiotic 2,4-diacetylphloroglucinol by the biological control agent Pseudomonas fluorescens Q2-87. MPMI 9 83 (1996). 

J. M. Raaijmakers, D. M. Weller, and L. S. Thomashow, Frequency of antibiotic producing Pseudomonas spp. in natural environments. Appk Environ. Microbiol. 63 881 (1997). 

---