Plasmid-mediated drug resistance of shigellae in Kuwait

Of 153 clinical isolates of shigellae examined, 64.7% belonged toShigella flexneri, 18.9% toSh. sonnei, 11.8% toSh. boydii and 4.6% toSh. dysenteriae. Part of these isolates were resistant to sulfamethoxazole and streptomycin (88.2% each), ampicillin (66.70, tetracycline (63.40 and co-trimoxazole (43.10, with levels of resistance (MIC₅₀ and MIC₉₀) being invariably high. Resistance to three or more drugs (multidrug resistance) was seen in 77.8% of the isolates. All the 25 strains examined for transfer of resistance contained R-plasmids, both autotransferable and non-autotransferable (mobilized by transfer factor X). The frequency of transfer of different r-determinants varied from 2.7 · 10^–8 to 1.4 · 10.     

Mechanisms of resistance to antibiotics

Microbial resistance to antibiotics is manifested by changes in antibiotic permeability, alteration of target molecules, enzymatic degradation of the antibiotics, and efflux of antimicrobials from the cytosol. Bacteria and other microorganisms use all of these mechanisms to evade the toxic effects of antibiotics. Recent research on the molecular aspects of these mechanisms, often informed by atomic resolution structures of proteins, enzymes and nucleic acids involved in these processes, has deepened our understanding of antibiotic action and resistance and, in several cases, spurred the development of strategies to overcome resistance in vitro and in vivo.     

Plasmid-determined streptococcal resistance to antibiotics]

The analysis of the genetic organization of the determinant ERLI by means of obtaining and studying the antibiotic sensitive mutants from the strain resistant to erythromycin and lincomycin provided experiment data in favour of the fact that inducable resistance to erythromycin and lincomycin determined by the plasmid might be defined by the same or closely linked genes.     

Beta-lactamases and bacterial resistance to antibiotics

The efficiency of β-lactam antibiotics, which are among our most useful chemotherapeutic weapons, is continuously challenged by the emergence of resistant bacterial strains. This is most often due to the production of β-lactamases by the resistant cells. These enzymes inactivate the antibiotics by hydrolysing the β-lactam amide bond. The elucidation of the structures of some β-lactamases by X-ray crystallography has provided precious insights into their catalytic mechanisms and revealed unsuspected similarities with the DD-transpeptidases, the bacterial enzymes which constitute the lethal targets of β-lactams. Despite numerous kinetic, structural and site-directed mutagenesis studies, we have not completely succeeded in explaining the diversity of the specificity profiles of β-lactamases and their surprising catalytic power. The solutions to these problems represent the cornerstones on which better antibiotics can be designed, hopefully on a rational basis.     

Antibiotic resistance of shigellae and rationale for etiotropic therapy of Shigella infections

The study was aimed at determining sensitivity of shigellae to antibacterial preparations and their clinical effectiveness for correcting recommendations on the empirical therapy of acute Shigella infections (ASI). The sensitivity of 164 S. flexneri strains and 80 S. sonnei strains, isolated in 1996-2003 in the Sumy region, Ukraine, was determined with respect to 19 antibacterial preparations: ampicillin (Am), tetracycline (Te), rifampicin (Ri), chloramphenicol (Ca), streptomycin (St), fusidin (Fu), kanamycin (Kn), erythromycin (Er), carbenicillin (Cb), doxycycline (Do), gentamicin (Ge), ofloxacin (Of), cefazolin (Cf), ciprofloxacin (Cp). S. flexneri and S. sonnei were found to be highly sensitive to Am (100%), Te (100%), Cb (90% and 50% respectively), Do (90% and 35% respectively), Fu (100%), Er (100%), Ri (100%), Ca (71.8% and 45% respectively), St (81% and 40% respectively). Some isolated cultures were resistant to fluorochinolones. In addition, the clinical and laboratory analysis of the effectiveness of some preparations was carried out. A total of 202 patients, divided into 6 groups, received furazolidone, chloramphenicol, norfloxacin, phthalazole, polymyxin and the combination of several antibacterial preparations. High efficiency of norfloxacin in the treatment of ASI was confirmed. The use of other preparations and their combinations was found to produce only a slight effect.     

Mechanism of natural resistance to kirromycin-type antibiotics in actinomycetes

Abstract The sensitivity of intact cells and subcellular fractions of actinomycetes to kirromycin and pulvomycin was examined. These antibiotics block bacterial protein synthesis by acting on elongation factor Tu (EF-Tu). Two types of natural resistance were encountered in actinomycetes. Some strains were resistant to kirromycin and pulvomycin by virtue of inefficient cellular uptake of these drugs. In 3 strains, kirromycin resistance was attributable to a drug-insensitive EF-Tu. These 3 organisms produce kirromycin-type antibiotics: Streptomyces cinnamomeus, Streptomyces lactamdurans and Streptoverticillium mobaraense synthesize kirrothricin, efrotomycin and pulvomycin, respectively. In S. cinnamomeus and S. lactamdurans resistance to their own antibiotic is due to possession of a nonresponding EF-Tu factor, whereas pulvomycin resistance in Sv. mobaraense is more likely derived from the permeability properties of the cell envelope.     

Reducing bacterial resistance to antibiotics with ultrasound

The effect of erythromycin on planktonic cultures of Psedomonas aeruginosa, with and without application of 70 kHz ultrasound, was studied. Ultrasound was applied at levels that had no inhibitory effect on cultures of Ps. aeruginosa. Ultrasound in combination with erythromycin reduced the viability of Ps. aeruginosa by 1-2 orders of magnitude compared with antibiotic alone, even at concentrations below the minimum inhibitory concentration (MIC). Electron-spin resonance studies suggest that ultrasound induces uptake of antibiotic by perturbing or stressing the membrane. This application of ultrasound may be useful for expanding the number of drugs available for treating localized infections by rendering bacteria susceptible to normally ineffective antibiotics.