Antibacterial and antibiofilm activities of thiazolidine‐2,4‐dione and 4‐thioxo‐thiazolidin‐2‐one derivatives against multidrug‐resistant Staphylococcus aureus clinical isolates

Abstract

Aims

Antimicrobial resistance is one of the highest priorities in global public health with Staphylococcus aureus among the most important microorganisms due to its rapidly evolving antimicrobial resistance. Despite all the efforts of antimicrobial stewardship, research and development of new antimicrobials are still imperative. The thiazolidine ring is considered a privileged structure for the development of new antimicrobials. This study aimed to compare the antibacterial effects of two analogue series of thiazolidine-2,4-dione and 4-thioxo-thiazolidin-2-one against multidrug-resistant Staph. aureus clinical isolates.

Methods and Results

The derivatives 1a, 2a and 2b exhibited MIC between 1–32 μg ml−1, with time-to-kill curves showing a bactericidal effect up to 24 h. In the antibiofilm assay, the most active derivatives were able to inhibit about 90% of biofilm formation. The 4-thioxo-thiazolidine-2-one derivatives were more active against planktonic cells, while the thiazolidine-2,4-dione derivatives were able to disrupt about 50% of the preformed biofilm. In the in vivo infection model using Caenorhabditis elegans as a host, the derivatives 1a, 2a and 2b increased nematode survival with a concentration-dependent effect. Exposure of Staph. aureus to the derivatives 2a and 2b induced surface changes and decrease cell size. None of the derivatives was cytotoxic for human peripheral blood mononuclear cells (PBMC) but showed moderate cytotoxicity for L929 fibroblasts.

Conclusion

The 5-(3,4-dichlorobenzylidene)-4-thioxothiazolidin-2-one (2b) was the most active derivative against Staph. aureus and showed higher selective indices.

Significance and Impact of the Study

4-thioxo-thiazolidin-2-one is a promising scaffold for the research and development of new antimicrobial drugs against multidrug-resistant Staph. aureus.

Prevalence, genetic diversity, antibiotic resistance and biofilm formation of Acinetobacter baumannii isolated from urban environments

Abstract

Aim

Acinetobacter baumannii is a well-known nosocomial pathogen that has been isolated from different clinical sources. This pathogen also causes community-acquired infections, with mortality rates as high as 64%. The exact natural habitat of this bacterium is still unknown. In this study, we investigated the prevalence of A. baumannii in diverse soil and high-touch surface samples collected from a university campus, malls, parks, hypermarkets and produce markets, roundabout playground slides and bank ATMs.

Methods and Results

All obtained isolates were characterized for their antibiotic susceptibility, biofilm formation capacities, and were typed by multi-locus sequence analysis. A total of 63 A. baumannii isolates were recovered, along with 46 Acinetobacter pittii and 8 Acinetobacter nosocomialis isolates. Sequence typing revealed that 25 A. baumannii isolates are novel strains. Toilets and sink washing basins were the most contaminated surfaces, accounting for almost 50% of the isolates. A number of A. baumannii (n = 10), A. pittii (n = 19) and A. nosocomialis (n = 5) isolates were recovered from handles of shopping carts and baskets. The majority of isolates were strong biofilm formers and 4 isolates exhibited a multi-drug resistant phenotype.

Conclusions

Our study is the first to highlight community restrooms and shopping carts as potential reservoirs for pathogenic Acinetobacter species. Further studies are required to identify the reasons associated with the occurrence of A. baumannii inside restrooms. Proper disinfection of community environmental surfaces and spreading awareness about the importance of hand hygiene may prevent the dissemination of pathogenic bacteria within the community.

Significance and Impact of the study

Serious gaps remain in our knowledge of how A. baumannii spreads to cause disease. This study will advance our understanding of how this pathogen spreads between healthcare and community environments. In addition, our findings will help healthcare decision-makers implement better measures to control and limit further transmission of A. baumannii.

Antimicrobial effects of automobile screen washes against Legionella pneumophila

Abstract

Aims

Legionella pneumophila (Lp), a human pathogen, has been detected in windscreen wiper fluid reservoirs (WWFRs) where commercial screen washes (CSWs) are commonly added. Limited information is available on CSWs against planktonic Lp; however, responses of sessile Lp and planktonic Lp pre-acclimated in nutrient-limited water to CSWs remain unknown. This study thus investigates the antibacterial effects of CSWs on sessile and starved planktonic Lp, in comparison with unstarved Lp.

Methods and Results

Lp biofilms were produced on glass and WWFR materials of high-density polyethylene (HDPE) and polypropylene (PP). Planktonic Lp with and without acclimation in tap water were prepared. Log reductions in cell counts averaged 0.4–5.0 for 10 brands of CSWs against sessile Lp and 1.0–3.9 and 0.9–4.9, respectively, against starved and unstarved planktonic Lp for five CSWs. Both biofilm formation and acclimation in tap water enhanced Lp resistance to CSWs. Significantly different log-reduction values among CSW brands were observed for sessile Lp on HDPE and planktonic Lp regardless of acclimation (p < 0.05).

Conclusions

Biofilm formation, starvation acclimation and CSW brand are crucial factors influencing Lp response to CSWs.

Significance and Impact of Study

This study advances the knowledge of Lp reaction in anthropogenic water systems with CSWs.

Dose–response analysis of Bacillus thuringiensis HD‐1 cry‐ spore reduction on surfaces using formaldehyde with pre‐germination

Abstract

Aim

To establish a basis for rapid remediation of large areas contaminated with Bacillus anthracis spores.

Methods and Results

Representative surfaces of wood, steel and cement were coated by nebulization with B. thuringiensis HD-1 cry- (a simulant for B. anthracis) at 5.9 ± 0.2, 6.3 ± 0.2 and 5.8 ± 0.2 log10 CFU per cm2, respectively. These were sprayed with formaldehyde, either with or without pre-germination. Low volume (equivalent to ≤2500 L ha−1) applications of formaldehyde at 30 g l−1 to steel or cement surfaces resulted in ≥4 or ≤2 log10 CFU per cm2 reductions respectively, after 2 h exposure. Pre-germinating spores (500 mmol l−1 l-alanine and 25 mmol l−1 inosine, pH 7) followed by formaldehyde application showed higher levels of spore inactivation than formaldehyde alone with gains of up to 3.4 log10 CFU per cm2 for a given dose. No loss in B. thuringiensis cry- viability was measured after the 2 h germination period, however, a pre-heat shock log10 reduction was seen for B. anthracis strains: LSU149 (1.7 log10), Vollum and LSU465 (both 0.9 log10), LSU442 (0.2 log10), Sterne (0.8 log10) and Ames (0.6 log10).

Conclusions

A methodology was developed to produce representative spore contamination of surfaces along with a laboratory-based technique to measure the efficacy of decontamination. Dose–response analysis was used to optimize decontamination. Pre-germinating spores was found to increase effectiveness of decontamination but requires careful consideration of total volume used (germinant and decontaminant) by surface type.

Significance and Impact of the Study

To be practically achievable, decontamination of a wide area contaminated with B. anthracis spores must be effective, timely and minimize the amount of materials required. This study uses systematic dose–response methodology to demonstrate that such an approach is feasible.