Resistance of Shigella to antibiotics

Antibiotic sensitivity of 104 Shigella clinical strains and 104 Escherichia coli strains isolated from patients with acute dysentery not treated with antibiotics in 1986-1987 was studied. It was shown that 100 per cent of the dysentery pathogens and colon bacilli were antibiotic resistant. Strains resistant simultaneously to chloramphenicol, ampicillin, streptomycin, tetracycline, monomycin and kanamycin were the most frequent among the dysentery pathogens. Colon bacilli and dysentery pathogens isolated from the same patient had specific sets of antibiotic resistance markers. Pathogenetic therapy of dysentery and exclusion of antibiotic use for several years did not result in lower numbers of Shigella antibiotic resistant strains.     

Sensitivity of Shigella to antibiotics]

Three hundred and twenty two Shigella cultures isolated from dysentery patients within 1986-1989 were tested with the use of standard paper disks for their sensitivity to levomycetin, streptomycin, tetracycline, monomycin, neomycin, kanamycin, erythromycin, gentamicin, carbenicillin, ampicillin, oxacillin, methicillin and doxycycline. The number of the cultures belonging to Shigella sonnei amounted to 85.1 per cent of the total number of the strains studied. 91.9, 89.5, 87.3, 87.3, 80.1 and 80.1 per cent of the cultures were sensitive to gentamicin, kanamycin, carbenicillin, neomycin, levomycetin and ampicillin, respectively. 99.4 per cent of the isolates were resistant to streptomycin and 97.2 per cent were resistant to tetracycline. The sensitivity to erythromycin remained rather high (70.2 per cent). The overwhelming majority of the Shigella sonnei isolates had multiple resistance.     

Increase in the sensitivity of Shigella to antibiotics

Passages of 10 Shigella strains for 10 times in meat-peptone broth supplemented with sodium nucleinate provided an increase in sensitivity of the cultures to levomycetin for a period of 264 hours. In three strains of S. sonnei, S. flexneri and S. newcastle the authors observed an increase in sensitivity to tetracycline, benzylpenicillin and streptomycin. Some nitrous bases included in sodium nucleinate were also able to increase antibiotic sensitivity in Shigella.     

Resistance of yeasts to polyene antibiotics

The strains of Saccharomyces cerevisiae yeast with mutations in two genes NYS3 NYS4 were obtained by tetrad analysis. Sterol fraction of these mutants contains two sterols: ergosta-7-en-3 beta-ol (fungisterol) and ergosta-7,24-dien-3 beta-ol (episterol). The findings allowed to testify the sequence of the ergosterol biosynthesis reactions. Dehydrogenization of the sterol nucleus in C5(6) which is controlled by gene NYS3 occurs simultaneously with the introduction of double bond in C22(23) site of the side chain regulated by gene NYS4.     

Resistance ofBradyrhizobium japonicum strains to selected antibiotics

The majority of the 50Bradyrhizobium japonicum strains tested were resistant to ampicillin, kanamycin, streptomycin and tetracycline in concentrations below 100 g/ml but resistant to chloramphenicol in concentrations equal to or above 100 g/ml. Two strains had high levels of resistance to ampicillin and to streptomycin and six strains were very sensitive to several antibiotics.

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Résumé La majorité de la cinquantaine de souches deBradyrhizobium japonicum s'est révélée résistante à l'ampicilline, à la kanamycine, à la streptomycine et à la tétracycline aux concentrations intérieures à 100g/ml mais au chloramphenicol aux concentrations égales ou supérieures à 100 g/ml. Deux souches présentalent un haut degré de résistance à l'ampicilline et à la streptomycine. Six souches étaient très sensibles à plusleurs antibiotiques.

     

Resistance ofPseudomonas aeruginosa to β-lactam antibiotics

A series of experiments were performed withP. aeruginosa to demonstrate which of the biochemical mechanisms are responsible for the resistance to the β-lactam antibiotics. The constitutive β-lactamase was isolated and characterized for the strain used as type OXA whose pI was 7.1, with a molar mass of 49 kg/mol. The strain was also submitted to a series of treatments with Tris and Tris -EDTA to disrupt the outer membrane. The treated cells demonstrated a ten-fold reduction in the MIC with cloxacillin, six-fold with penicillin, and five-fold with oxacillin. At least two different biochemical mechanisms were responsible for the resistance to the β-lactams studied which could be important in the prevalence ofP. aeruginosa in nosocomial infections.     

Resistance of hospital Staphylococci to beta-lactam antibiotics]

Resistance of hospital Staphylococci to beta-lactam antibiotics was studied. The strains were isolated in two obstetric hospitals during an outbreak of purulent inflammatory infections in them. A modification of the "clover leaf" procedure providing elucidation of the resistance mechanism was used in the study. Development of the resistance to the beta-lactam antibiotics was shown to be mainly due the activity of beta-lactamases which makes it possible to discuss their role in the mechanism of resistance development.     

Resistance to antibiotics targeted to the bacterial cell wall

Peptidoglycan is the main component of the bacterial cell wall. It is a complex, three‐dimensional mesh that surrounds the entire cell and is composed of strands of alternating glycan units crosslinked by short peptides. Its biosynthetic machinery has been, for the past five decades, a preferred target for the discovery of antibacterials. Synthesis of the peptidoglycan occurs sequentially within three cellular compartments (cytoplasm, membrane, and periplasm), and inhibitors of proteins that catalyze each stage have been identified, although not all are applicable for clinical use. A number of these antimicrobials, however, have been rendered inactive by resistance mechanisms. The employment of structural biology techniques has been instrumental in the understanding of such processes, as well as the development of strategies to overcome them. This review provides an overview of resistance mechanisms developed toward antibiotics that target bacterial cell wall precursors and its biosynthetic machinery. Strategies toward the development of novel inhibitors that could overcome resistance are also discussed.