Surface adherence and vacuolar internalization of bacterial pathogens to the Candida spp. cells: Mechanism of persistence and propagation.

BACKGROUND: The co-existence of Candida albicans with the bacteria in the host tissues and organs displays interactions at competitive, antagonistic, and synergistic levels. Several pathogenic bacteria take advantage of such types of interaction for their survival and proliferation. The chemical interaction involves the signaling molecules produced by the bacteria or Candida spp., whereas the physical attachment occurs by involving the surface proteins of the bacteria and Candida. In addition, bacterial pathogens have emerged to internalize inside the C. albicans vacuole, which is one of the inherent properties of the endosymbiotic relationship between the bacteria and the eukaryotic host. AIM OF REVIEW: The interaction occurring by the involvement of surface protein from diverse bacterial species with Candida species has been discussed in detail in this paper. An in silico molecular docking study was performed between the surface proteins of different bacterial species and Als3P of C. albicans to explain the molecular mechanism involved in the Als3P-dependent interaction. Furthermore, in order to understand the specificity of C. albicans interaction with Als3P, the evolutionary relatedness of several bacterial surface proteins has been investigated. Furthermore, the environmental factors that influence bacterial pathogen internalization into the Candida vacuole have been addressed. Moreover, the review presented future perspectives for disrupting the cross-kingdom interaction and eradicating the endosymbiotic bacterial pathogens. KEY SCIENTIFIC CONCEPTS OF REVIEW: With the involvement of cross-kingdom interactions and endosymbiotic relationships, the bacterial pathogens escape from the environmental stresses and the antimicrobial activity of the host immune system. Thus, the study of interactions between Candida and bacterial pathogens is of high clinical significance.

Inhibition of biofilm and virulence properties of Pseudomonas aeruginosa by sub-inhibitory concentrations of aminoglycosides.

Aminoglycosides are a commonly used class of antibiotics; however, their application has been discontinued due to the emergence of multi-drug resistance bacterial strains. In the present study, the subinhibitory concentrations (sub-MIC) of several aminoglycosides were determined and tested as an antibiofilm and for their anti-virulence properties against Pseudomonas aeruginosa PAO1, which is an opportunistic foodborne pathogen. P. aeruginosa PAO1 exhibits multiple mechanisms of resistance, including the formation of biofilm and production of several virulence factors, against aminoglycoside antibiotics. The sub-MIC of these antibiotics exhibited biofilm inhibition of P. aeruginosa in alkaline TSB (pH 7.9). Moreover, various concentrations of these aminoglycosides also eradicate the mature biofilm of P. aeruginosa. In the presence of sub-MIC of aminoglycosides, the morphological changes of P. aeruginosa were found to change from rod-shaped to the filamentous, elongated, and streptococcal forms. Similar growth conditions and sub-MIC of aminoglycosides were also found to attenuate several virulence properties of P. aeruginosa PAO1. Molecular docking studies demonstrate that these aminoglycosides possess strong binding properties with the LasR protein, which is a well-characterized quorum-sensing receptor of P. aeruginosa. The present study suggests a new approach to revitalize aminoglycosides as antibiofilm and antivirulence drugs to treat infections caused by pathogenic bacteria.

Functional Diversity of Quorum Sensing Receptors in Pathogenic Bacteria: Interspecies, Intraspecies and Interkingdom Level.

The formation of biofilm by pathogenic bacteria is considered as one of the most powerful mechanisms/modes of resistance against the action of several antibiotics. Biofilm is formed as a structural adherent over the surfaces of host, food and equipments etc. and is further functionally coordinated by certain chemicals produced itself. These chemicals are known as quorum sensing (QS) signaling molecules and are involved in the cross talk at interspecies, intraspecies and interkingdom levels thus resulting in the production of virulence factors leading to pathogenesis. Bacteria possess receptors to sense these chemicals, which interact with the incoming QS molecules. It is followed by the secretion of virulence molecules, regulation of bioluminescence, biofilm formation, antibiotic resistance development and motility behavioral responses. In the natural environment, different bacterial species (Gram-positive and Gram-negative) produce QS signaling molecules that are structurally and functionally different. Recent and past research shows that various antagonistic molecules (naturally and chemically synthesized) are characterized to inhibit the formation of biofilm and attenuation of bacterial virulence by blocking the QS receptors. This review article describes about the diverse QS receptors at their structural, functional and production levels. Thus, by blocking these receptors with inhibitory molecules can be a potential therapeutic approach to control pathogenesis. Furthermore, these receptors can also be used as a structural platform to screen the most potent inhibitors with the help of bioinformatics approaches.