One of the reasons for increased antibiotic resistance in Salmonella
enterica serovar Typhi Ty2 is the influx of heavy
metal ions in the sewage, from where the infection is transmitted.
Therefore, curbing these selective agents could be
one of the strategies to manage the emergence of multidrug
resistance in the pathogen. As observed in our earlier study,
the present study also confirmed the links between cadmium
accumulation and antibiotic resistance in Salmonella. Therefore,
the potential of a chemically-synthesised compound 2,
2-dipyridyl diselane (DPDS) was explored to combat the
metal-induced antibiotic resistance. Its metal chelating and
antimicrobial properties were evidenced by fourier transform
infrared spectroscopy (FTIR), field emission scanning
electron microscopy (FE-SEM), and microbroth dilution method . Owing to these properties of DPDS, further, this
compound was evaluated for its potential to be used in combination
with conventional antibiotics. The data revealed
effective synergism at much lower concentrations of both
the agents. Thus, it is indicated from the study that the combination
of these two agents at their lower effective doses
might reduce the chances of emergence of antibiotic resistance,
which can be ascribed to the multi-pronged action of
the agents.
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Farnesol is a quorum-sensing molecule that inhibits biofilm
formation in Candida albicans. Previous in vitro data suggest
that, in combination with certain antifungals, farnesol
may have an adjuvant anti-biofilm agent. However, the in
vivo efficacy of farnesol is very questionable. Therefore, the
in vitro and in vivo activity of fluconazole combined with farnesol
was evaluated against C. albicans biofilms using fractional
inhibitory concentration index (FICI) determination,
time-kill experiments and a murine vulvovaginitis model.
The median biofilm MICs of fluconazole-sensitive C. albicans
isolates ranged between 4 -> 512 mg/L and 150–300 μM
for fluconazole and farnesol, respectively. These values were
512 -> 512 mg/L and > 300 μM for fluconazole-resistant clinical
isolates. Farnesol decreased the median MICs of fluconazole
by 2-64-fold for biofilms. Based on FICI, synergistic
interaction was observed only in the case of the sessile
SC5314 reference strain (FICIs: 0.16–0.27). In time-kill studies,
only the 512 mg/L fluconazole and 512 mg/L fluconazole
+ 75 μM farnesol reduced biofilm mass significantly at
each time point in the case of all isolates. The combination
reduced the metabolic activity of biofilms for all isolates in a
concentration- and time-dependent manner. Our findings
revealed that farnesol alone was not protective in a murine
vulvovaginitis model. Farnesol was not beneficial in combination
with fluconazole for fluconazole-susceptible isolates,
but partially increased fluconazole activity against one fluconazole-
resistant isolate, but not the other one.
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Communities of microbes can live almost anywhere and contain many different species. Interactions between members of these communities often determine the state of the habitat in which they live. When these habitats include sites on the human body, these interactions can affect health and disease. Polymicrobial synergy can occur during infection, in which the combined effect of two or more microbes on disease is worse than seen with any of the individuals alone.
Powerful genomic methods are increasingly used to study microbial communities, including metagenomics to reveal the members and genetic content of a community and metatranscriptomics to describe the activities of community members. Recent efforts focused toward a mechanistic understanding of these interactions have led to a better appreciation of the precise bases of polymicrobial synergy in communities
containing bacteria, eukaryotic microbes, and/or viruses. These studies have benefited from advances in the development of in vivo models of polymicrobial infection and modern techniques to profile the spatial and chemical bases of intermicrobial communication. This review describes the breadth of mechanisms microbes use to interact in ways that impact pathogenesis and techniques to study polymicrobial communities.
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