Search

The increase in the number of bacteria that are resistant to multiple antibiotics poses a serious clinical problem that threatens the health of humans worldwide. Nadifloxacin ( 1 ) is a highly potent antibacterial agent with broad-spectrum activity. However, its poor aqueous solubility has limited its use to topical applications. To increase its solubility, it was glycosylated herein to form a range of trans -linked ( 3a-e ) and cis -linked ( 7a,b ) glycosides, each of which was prepared and purified to afford single anomers. The seven glycoside derivatives ( 3a-e, 7a,b ) were examined for potency against eight strains of S. aureus , four of which were methicillin-resistant. Although less potent than free nadifloxacin ( 1 ), the α-L-arabinofuransoside ( 3a ) was effective against all strains that were tested (minimum inhibitory concentrations of 1-8 μg/mL compared to 0.1-0.25 μg/mL for nadifloxacin), demonstrating the potential of this glycoside as an antibacterial agent. Estimation of Log P as well as observations made during preparation of these compounds reveal that the solubilities of the glycosides were greatly improved compared with nadifloxacin ( 1 ), raising the prospect of its use in oral applications.

There is an ongoing urgent need for new targeted antibacterial compounds with novel mechanisms of action for the treatment of infections caused by bacteria that are resistant to currently available materials. Since the expression of glycosidase enzymes within bacteria is unequally distributed, glycoside derivatives of antibacterial agents offer potential as targeted prodrugs for bacterial infections. Herein we report the synthesis and characterisation of four α-D-glycopyranosides and three β-D-glycopyranosides of the broad antibacterial agent triclosan, in generally good synthetic yields, and with excellent purities. Each glycoside was analysed to determine its ability to inhibit the growth of a wide range of Gram-negative and Gram-positive organisms, including many of clinical significance. All of the triclosan glycosides that were synthesized demonstrated antibacterial activity against many of the organisms that were examined. For example, β-galactoside (3a) and α-arabinoside (3c) had MIC values of 0.5 μg/ml for several strains of S. aureus and S. haemolyticus. The triclosan glycosides were also generally found to be more water soluble and much more selective than the underivatized triclosan, making them ideal both for the targeted inhibition of bacterial growth and as agents for the selective recovery of bacteria from mixed cultures. In the latter case, two Bacillus strains could be identified from various strains of Bacillus and Staphylococcus after inoculation onto Nutrient Agar No. 2 with 0.25 μg/ml triclosan-α-D-glucopyranoside (3e). This glucoside may, therefore, be of use for the isolation and identification of the food-poisoning organism Bacillus cereus., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

When Campylobacter jejuni cultures that had been grown in broth at 39 degrees C were subcultured into fresh medium at 30 degrees C, there was a transient period of growth followed by a decline in viable-cell numbers before growth resumed once more. We propose that this complex behavior is the net effect of the growth of inoculum cells followed by a loss of viability due to oxidative stress and the subsequent emergence of a spontaneously arising mutant population that takes over the culture.

Growth of Listeria monocytogenes and Salmonella was examined during various rates of increase and decrease in temperature from and to the minimum for growth. Growth was little affected by even the most rapid changes and injury or lag was not observed. Subsequent investigations of growth during periods of rapid variation in temperature from and to temperatures below the growth minimum again had little effect and growth was satisfactorily predicted using the dynamic model of Baranyi and Roberts [Int. J. Food Microbiol. 23 (1994) 277] in conjunction with the data of Food Micromodel.

When stationary phase batch cultures of Campylobacter jejuni were stored in sealed flasks under static conditions, viable numbers declined from 2 x 10(9) c.f.u. ml-1 to around 10(3)-10(6) c.f.u. ml-1 within 4-6 weeks. When the aged cultures were sparged with a microaerobic gas mixture, there was a rapid increase in viable numbers accompanied by a change from predominantly coccoid to vibrioid morphology. The most probable number (MPN) technique was used to distinguish resuscitation of injured or dormant cells from multiplication of residual viable cells. MPN estimates using fresh Brucella broth containing 0.2% mucin revealed that plate counts underestimated the true viable count by up to 23-fold. The experiments clearly demonstrated that a proportion of surviving cells in aged cultures were in an injured or latent state that prevented growth on agar plates. It is possible that the size of this fraction is greater than was demonstrated and that much higher recoveries would be obtained under other recovery conditions. Nevertheless, from presently available evidence, it must be concluded that the size of the latent fraction is quite small and that most of the increase in count that occurs on regassing a spent culture comes from multiplication of residual viable cells.

The fluorogenic redox indicator 5-cyano-2,3-ditolyltetrazolium chloride (CTC) was compared with the chromogenic p-iodonitrotetrazolium violet (INT) and conventional methods to assess cellular viability. Mild heat treatment was used as well-controlled method for producing non-viable and sub-lethally injured cells. CTC gave an underestimation of the viability of Listeria monocytogenes cells when compared with classical plating methods whereas INT gave an overestimation. However, CTC proved to be a sensitive indicator of uninjured cells. The difference between the total count and the CTC count was equivalent to the injured cell population. The fluorescent formazan formed on reduction of CTC was readily detected with a charge coupled device and cells enumerated automatically using image analysis.