Revisiting the virulence hallmarks of Pseudomonas aeruginosa: a chronicle through the perspective of quorum sensing

Abstract

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.

Epidemiology, Molecular Characteristics, and Virulence Factors of Carbapenem-Resistant Pseudomonas aeruginosa Isolated from Patients with Urinary Tract Infections

“… 13 , 14 Meanwhile, hemolytic phospholipase C (PlcH) and nonhemolytic phospholipase C (PlcN) hydrolyze various phospholipids of the host cell membrane: PlcH hydrolyzes host-associated phosphatidylcholine and the sphingomyelin and PlcN hydrolyzes phosphatidylserine and phosphatidylcholine. 15 In addition, LasB elastase degrades the structural proteins of cells such as collagen, non-collagen proteins, and elastin, and LasA protease enhances the elastolytic activity of LasB. 13 , 15 Alkaline protease (AprA) is a secreted zinc metalloprotease that degrades components of the host immune system, such as the complement system proteins (C1q, C2, C3), cytokines (IFN-γ, TNF-α), and components of the extracellular matrix (laminins, basal lamina) for tissue invasion and dissemination.…”

“… 15 In addition, LasB elastase degrades the structural proteins of cells such as collagen, non-collagen proteins, and elastin, and LasA protease enhances the elastolytic activity of LasB. 13 , 15 Alkaline protease (AprA) is a secreted zinc metalloprotease that degrades components of the host immune system, such as the complement system proteins (C1q, C2, C3), cytokines (IFN-γ, TNF-α), and components of the extracellular matrix (laminins, basal lamina) for tissue invasion and dissemination. 13 , 15 Furthermore, pyoverdin (fluorescein), encoded by the pvdA gene, is a fluorescent yellow-green siderophore that facilitates the uptake of iron for the survival and growth of P. aeruginosa under conditions of iron limitation.…”

“… 13 , 15 Alkaline protease (AprA) is a secreted zinc metalloprotease that degrades components of the host immune system, such as the complement system proteins (C1q, C2, C3), cytokines (IFN-γ, TNF-α), and components of the extracellular matrix (laminins, basal lamina) for tissue invasion and dissemination. 13 , 15 Furthermore, pyoverdin (fluorescein), encoded by the pvdA gene, is a fluorescent yellow-green siderophore that facilitates the uptake of iron for the survival and growth of P. aeruginosa under conditions of iron limitation. 16 On the other hand, pyocyanin, a blue-green phenazone-derivative pigment, is involved in the inflammatory response and tissue damage during pathogenesis by inducing cell apoptosis via increasing the levels of reactive oxygen species.…”

Toxoflavin secreted byPseudomonas alcaliphilainhibits growth ofLegionella pneumophilaand its hostVermamoeba vermiformis

“…To our knowledge, regulation of toxoflavin production by temperature has not been reported in Pseudomonas spp. However, Pseudomonas is recognized for having complex quorum sensing systems, which have been studied extensively in (Chadha et al, 2021). Therefore, the regulation of toxoflavin production by quorum sensing could explain this result.…”

The Role of Pseudomonas aeruginosa Virulence Factors in Cytoskeletal Dysregulation and Lung Barrier Dysfunction

“…Quorum sensing (QS) is a specialized cell density-dependent regulation system in bacteria [141][142][143]. These bacterial signals also modulate mammalian airway epithelial cell responses to the pathogen in a process called interkingdom signaling.…”