Pseudomonas aeruginosa is an opportunistic pathogen and the leading cause of mortality among immunocompromised patients in clinical setups. The hallmarks of virulence in P. aeruginosa encompass six biologically competent attributes that cumulatively drive disease progression in a multistep manner. These multifaceted hallmarks lay the principal foundation for rationalizing the complexities of pseudomonal infections. They include factors for host colonization and bacterial motility, biofilm formation, production of destructive enzymes, toxic secondary metabolites, iron-chelating siderophores and toxins. This arsenal of virulence hallmarks is fostered and stringently regulated by the bacterial signalling system called quorum sensing (QS). The central regulatory functions of QS in controlling the timely expression of these virulence hallmarks for adaptation and survival drive the disease outcome. This review describes the intricate mechanisms of QS in P. aeruginosa and its role in shaping bacterial responses, boosting bacterial fitness. We summarize the virulence hallmarks of P. aeruginosa, relating them with the QS circuitry in clinical infections. We also examine the role of QS in the development of drug resistance and propose a novel antivirulence therapy to combat P. aeruginosa infections. This can prove to be a next-generation therapy that may eventually become refractory to the use of conventional antimicrobial treatments.
Summary
Unregulated consumption and overexploitation of antibiotics have paved the way for emergence of antibiotic‐resistant strains and ‘superbugs’. Pseudomonas aeruginosa is among the opportunistic nosocomial pathogens causing devastating infections in clinical set‐ups globally. Its artillery equipped with diversified virulence elements, extensive antibiotic resistance and biofilms has made it a ‘hard‐to‐treat’ pathogen. The pathogenicity of P. aeruginosa is modulated by an intricate cell density‐dependent mechanism called quorum sensing (QS). The virulence artillery of P. aeruginosa is firmly controlled by QS genes, and their expression drives the aggressiveness of the infection. Attempts to identify and develop novel antimicrobials have seen a sharp rise in the past decade. Among different proposed mechanisms, a novel anti‐virulence approach to target pseudomonal infections by virtue of anti‐QS and anti‐biofilm drugs appears to occupy the centre stage. In this respect, bioactive phytochemicals have gained prominence among the scientific community owing to their significant quorum quenching (QQ) properties. Recent studies have shed light on the QQ activities of various phytochemicals and other drugs in perturbing the QS‐dependent virulence in P. aeruginosa. This review highlights the recent evidences that reinforce the application of plant bioactives for combating pseudomonal infections, their advantages and shortcomings in anti‐virulence therapy.
Just when the world started to adapt to the ‘new normal’ amid the coronavirus disease 19 (COVID‐19) pandemic, the world is witnessing the wrath of another viral disease, the monkeypox virus (MPXV). The virus is endemic to African countries, where several outbreaks have been reported in the past. However, the present cases have been reported in non‐endemic countries worldwide. Although MPX is considered to be a self‐limiting disease, recent reports on its incidence have proved otherwise. The 2022 multi‐country MPX outbreak has drawn the attention of global surveillance organizations and epidemiologists to trace its origin; however, there are existing gaps regarding the animal reservoirs, biological implications, and management of MPX. In view of the recent events, the World Health Organization (WHO) has also declared the ongoing MPX outbreak a global health emergency. Hence, the geographically expanding MPXV poses a significant threat to human health and public safety. In this review, the latest insights into the biology of MPXV have been provided by discussing its biological implications on human health, changing epidemiological footprint, and presently available intervention strategies. This review also sheds light on the existing lacunas and possible reasons that may have been responsible for the ongoing MPX outbreak.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging respiratory virus responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic. More than a year into this pandemic, the COVID-19 fatigue is still escalating and takes hold of the entire world population. Driven by the ongoing geographical expansion and upcoming mutations, the COVID-19 pandemic has taken a new shape in the form of emerging SARS-CoV-2 variants. These mutations in the viral spike (S) protein enhance the virulence of SARS-CoV-2 variants by improving viral infectivity, transmissibility and immune evasion abilities. Such variants have resulted in cluster outbreaks and fresh infection waves in various parts of the world with increased disease severity and poor clinical outcomes. Hence, the variants of SARS-CoV-2 pose a threat to human health and public safety. This review enlists the most recent updates regarding the presently characterized variants of SARS-CoV-2 recognized by the global regulatory health authorities (WHO, CDC). Based on the slender literature on SARS-CoV-2 variants, we collate information on the biological implications of these mutations on virus pathology. We also shed light on the efficacy of therapeutics and COVID-19 vaccines against the emerging SARS-CoV-2 variants.
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