Effect of fosfidomycin on development of various infections in mice]

Antibiotic fosmidomycin will know as inhibitor of the nonmevalonate pathway of isoprenoid biosynthesis and as possible antimalarial drug, was shown to possess a certain protective effect on mice experimentally infected with tularemia, tiphus or coli-septicemia. Positive effect on mice with chronic form of tuberculosis was not observed when the animals were given 1 mg of fosmidomycin per capita twice a day. Under oxidative conditions an ESR signal of long living nitroxil free radicals were registered in the water solution of fosmidomycin. The radicals are supposed to be involved in the therapeutic effect of the antibiotic.     

Effect of volatiles from bacteria and yeast on the growth and pigmentation of sapstain fungi

Sapstain fungi affect the appearance of wood due to colonisation by pigmented hyphae but without producing significant strength losses. This is due to the production of melanin in the fungal cell walls of the staining fungi. Any biological control strategy targeted against this type of deterioration would therefore be considered successful if it inhibited either fungal growth or pigment production. Previous work has established that specific bacterial and yeast isolates selected on the basis of agar screening studies could significantly reduce levels of staining in wood block tests. This paper presents the results of a study to examine the role of volatile organic compounds (VOCs) produced by four bacterial and three yeast isolates on the growth and pigment production by a range of five sapstain fungi on three media types. VOCs from three of the four bacterial strains tested completely inhibited growth of the five target sapstain fungi but only when the antagonists were grown on tryptone soya media. When antagonists were grown on either malt agar or a low nutrient medium levels of inhibition were either significantly reduced or non-existent. Yeast antagonists generally produced lower levels of growth inhibition than the bacteria but a Williopsis mrakii isolate gave 100% inhibition of three of the five sapstain fungi. Production of inhibitory VOCs was highly dependent on the specific antagonist as well as its growth substrate and all five sapstain fungi showed varying sensitivities to the VOCs produced. Not all fungi were inhibited, growth of O. piliferum and A. pullulans being stimulated by the VOCs from antagonists but only when grown under low nutrient conditions. In some instances, where growth was only slightly reduced, the level of pigmentation of the sapstain colony was significantly reduced compared with corresponding controls. The implications of this work for the biological control of sapstain fungi are discussed.     

Antibiotic susceptibility of bacterial strains isolated from patients with various infections

AIMS: Isolates from various samples obtained during 1998 and 1999 were identified and their susceptibility to third-generation cephalosporins, monobactams and/or cephamycins studied along with any production of ESBLs. METHODS AND RESULTS: Of these samples, bacteria most frequently isolated by the conventional techniques and Vitek GNI card were Escherichia coli (37%), Klebsiella pneumoniae (27%) and Enterobacter cloacae (16%). Using disk diffusion and double-disk synergy tests, we found that 71% strains produced ESBLs and 18% strains produced ESBLs and cephamycinases. Banding patterns of PCR amplification with the designed primers showed that 57% strains were capable of harbouring bla(SHV) genes. The bla(TEM), bla(CMY) and bla(AmpC) genes were harboured by 55%, 31% and 12% strains, respectively. Forty-five percent of strains contained more than two types of beta-lactamase genes. In particular, one strain contained bla(TEM), bla(SHV), bla(CMY) and bla(AmpC) genes. CONCLUSIONS: The percentage of ESBL-producing strains was high. The most prevalent beta-lactamase gene was bla(SHV) gene. The bla(CMY) genes have been prevalent in cephamycin-resistant strains. The multidrug-resistant strains resistant to third-generation cephalosporins and cephamycins were detected in high percentage. SIGNIFICANCE AND IMPACT OF THE STUDY: Resistance mechanisms to beta-lactams, comprising mostly extended-spectrum beta-lactamase (ESBL) production, lead to the resistance against even recently developed beta-lactams in enterobacteria, which is now a serious threat to antibiotic therapy. The high prevalence of bla(CMY) genes and multidrug-resistant genes may also cause therapeutic failure and lack of eradication of these strains by third-generation cephalosporins or cephamycins.     

Polymorphonuclear leukocytes and innate immunity to Salmonella infections in mice.

Neutropenia makes normal mice more susceptible to infection with spv (+) but not spv (-) Salmonella dublin. This shows the important role of polymorphonuclear leukocytes in resistance to Salmonella that can grow in host macrophages. Polymorphonuclear leukocytes, part of the innate immune system, kill Salmonella in a complement-dependent manner, and work in concert with macrophages.     

Immunoadjuvant activities of cell walls and their water-soluble fractions prepared from various gram-positive bacteria.

The cell walls from all 21 species of gram-positive bacteria examined, except lysozyme-susceptible Micrococcus lysodeikticus (NCTC 2665) and lysozyme-resistant Staphylococcus epidermidis (ATCC 155), were found to be definitely adjuvant-active in both stimulation of increased serum antibody levels and induction of delayed-type hypersensitivity to ovalbumin when administered to guinea-pigs as water-in-oil emulsions. Using various cell wall lytic enzymes, the immunoadjuvant principles were solubilized with full retention of the adjuvant activities from walls of Staphylococcus aureus (Copenhagen), Streptococcus pyogens (group A, type 6; S43/100), Streptococcus salivarius (IFO 3350), Streptococcus faecalis (IFO 12580), Streptococcus mutans (BHT), Lactobacillus plantarum (ATCC 8014), Bacillus megaterium (IFO 12068), Corynebacterium diphtheriae (Park-Williams No. 8), Mycobacterium smegmatis, and Actinomyces viscous (ATCC 15987). Evidence was obtained that the non-peptidoglycan portion of the cell walls is not essential for manifestation of immunoadjuvancy.     

Leukocyte agglomeration test to reveal bacterial infections in mice

A simple and rapid procedure was used to detecting covert bacterial infections in mice. The procedure was based on observations that bacterial infections were associated with clumping of leukocytes. A large drop of citrated venous blood was placed on a slide and allowed to spread. After fixation and staining the percentage of agglomerated leukocytes was determined by counting. Experimental urinary tract infections caused by either Escherichia coli or Proteus mirabilis served as a model to test the efficacy of the method. Elevation of leukocyte agglomeration was observed in these localized infections.     

Cell-mediated immunity to vesicular stomatitis virus infections in mice.

The T cell-mediated immune responses of mice against vesicular stomatitis virus (VSV) were assessed by measuring direct primary foot pad swelling after local VSV infection and cytotoxic activity in spleens. The cytolytic activity was mediated by T cells since it was anti-theta + complement sensitive, was restricted by the K and D region but not the I region of H-2 and rapidly increased after 4 days but decreased 8 days after systemic or local infection. Cytolytic activity was virus-specific as reciprocally tested with VSV and vaccina virus immune T cells. Measurable activity on day 7 depended on infectious virus dose, virus virulence, and non-H-2 genetic background of the host. More than half of the cytolytic activity wasblocked specifically by either immune anti-H2 or rabbit anti-VSV antisera. Analysis of the kinetics of appearance of antigenic changes using metabolic inhibitors, revealed that the changes that rendered target cells susceptible to lysis after infection, occurred within the first hour after infection.     

Nematospiroides dubius: genetic control of immunity to infections of mice

Inbred strains of mice differ in their susceptibility and resistance to challenge infections with Nematospiroides dubius. In our studies, F1 hybrid mice from resistant SJL and susceptible CBA parents were resistant to N. dubius challenge infections. Only 22% of backcrosses to SJL were susceptible while backcrosses to CBA had a wide range of susceptibility. Male mice were more susceptible than female mice. In another experiment, inbred strains of mice were compared in their ability to resist N. dubius challenge infection: SJL and A.SW (H-2s) mice became resistant after one immunizing infection, A, A/He (both H-2a), as well as BALB/c and DBA/2 (both H-2d) mice became resistant after two immunizing infections, while C57BL/6 (H-2b), C3H/He, CBA, and AKR (H-2k) mice remained susceptible. The resistance to reinfections was characterized by reduction of worm burdens between Days 6 and 14 postinfection. It was concluded that (1) resistance to N. dubius challenge infections is inherited in a dominant fashion and that multiple genes may influence such response, which in turn might be modulated by the Y chromosome; (2) both MHC and non-MHC genes may influence, in conjunction with the number of exposures to parasite antigens, the resistance to challenge infections.