Role of Pyocyanin and Extracellular DNA in Facilitating Pseudomonas aeruginosa Biofilm Formation
By Theerthankar Das, Amaye I. Ibugo, William Klare and Mike
Pseudomonas aeruginosa is an opportunistic Gram‐negative bacterium that is primarily responsible for infections related to cystic fibrosis (CF) airways, burn wounds, urinary tract infections, surgery‐associated infections, and HIV‐related illness. Pyocyanin and extracellular DNA (eDNA) are the major factors dictating the progression of biofilm formation and infection. Pyocyanin is a potent virulence factor causing cell death in infected CF patients and is associated with high mortality. eDNA is a key player in P. aeruginosa biofilm formation and is also responsible for the high viscosity of CF sputum that blocks the respiratory airway passages. In this chapter, we summarize our recent findings on the role of pyocyanin in facilitating P. aeruginosa biofilm formation. Pyocyanin promotes eDNA release in P. aeruginosa by inducing cell lysis mediated via hydrogen peroxide (H2O2) production. Pyocyanin intercalates with the nitrogenous bases of DNA and creates structural perturbation on the double‐helix structure. Pyocyanin‐eDNA binding significantly influences P. aeruginosa cell surface hydrophobicity and influences the physicochemical interactions facilitating bacterial cell‐to‐cell interaction (aggregation) and ultimately facilitates robust biofilm formation. A pyocyanin knockout (ΔphzA‐G) mutant is shown to have significantly reduced eDNA release and biofilm formation in comparison to its wild‐type. To this end, we discover that antioxidant glutathione directly binds to pyocyanin and modulates pyocyanin structure and function, thus inhibiting pyocyanin‐eDNA binding and consequently hampering biofilm development.
Part of the book: Microbial Biofilms
Pseudomonas aeruginosa Extracellular Secreted Molecules Have a Dominant Role in Biofilm Development and Bacterial Virulence in Cystic Fibrosis Lung Infections
By Theerthankar Das and Jim Manos
Cystic fibrosis (CF) is a genetic disorder that predominantly affects Caucasian populations. Pseudomonas aeruginosa is the most important Gram‐negative pathogen that persists in CF patients’ lungs. By evading host defence mechanisms and persisting, it is ultimately responsible for the morbidity and mortality of about 80% of CF patients worldwide. P. aeruginosa is also responsible for infections in burns, wounds, eyes, nosocomial patients and HIV patients. Prevalence and progression of infection by P. aeruginosa in the host is dependent on secretion of numerous extracellular molecules such as polysaccharides, proteases, eDNA, pyocyanin and pyoverdine. These molecules have multiple roles in facilitating P. aeruginosa colonisation and virulence. Pyocyanin is one of the major factors dictating progression of infection and biofilm formation. Pyocyanin is a potent virulence factor causing host cell death in CF patients. In this chapter, we have outlined the roles of various extracellular molecules secreted by P. aeruginosa and specifically focused on the role of pyocyanin in inducing eDNA production, binding to eDNA via intercalation and facilitating biofilm promoting factors, whilst inducing oxidative stress to host cells via production of reactive oxygen species. In line with this, we have described the current challenges in treatment of CF infections and the development of new strategies to control P. aeruginosa infections.
Part of the book: Progress in Understanding Cystic Fibrosis
Pseudomonas aeruginosa Secreted Biomolecules and Their Diverse Functions in Biofilm Formation and Virulence
By Theerthankar Das
Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium accountable for causing life-threatening infections in humans. According to the World Health Organization, P. aeruginosa classified as a critical pathogen. Specifically, P. aeruginosa in its colonized or biofilm state presents a major infection threat to immunocompromised (HIV) patients, Cystic fibrosis, burns, wounds and surgery associated infection. It is also a common pathogen responsible for causing hospital acquired/nosocomial infection and Urinary tract infections. P. aeruginosa biofilm is made up of bacterial self-synthesized biomolecules includes extracellular DNA, polysaccharides, proteins, RNA, siderophores and metabolites such as pyocyanin. This chapter will elaborate the manifold functions of P. aeruginosa secreted biomolecules in establishing and stabilizing biofilms, triggering virulence and pathogenicity in host, and resisting antibiotics and antibacterial agents.
Part of the book: Pseudomonas aeruginosa
Biofilm Formation by Pathogenic Bacteria: The Role of Quorum Sensing and Physical - Chemical Interactions View all chapters
By Theerthankar Das and Brandon C. Young
Pathogenic bacteria cause infectious diseases, mainly when the host (humans, animals, and plants) are colonised by bacteria, especially in its biofilm stage, where it is known to cause chronic infections. Biofilms are associated with resistance to antimicrobial agents, including antibiotics, antiseptics, detergents, and other therapeutic approaches. Antimicrobial resistance (AMR) is one of the biggest public health challenges of our time and is termed a ‘silent pandemic’ by the United Nations. Biofilm formation, pathogenicity and the associated AMR are regulated through a bacterial cell-to-cell communication system termed “Quorum Sensing (QS)’. As the bacterial cells sense the fluctuations in their population, they biosynthesise and secrete the signalling molecules called autoinducers (AI). In gram-negative, the signalling molecules are primarily homoserine lactones (AHL) whereas in gram-positive the signalling molecules are autoinducing peptides. The AI binds to receptor and regulator proteins in the bacterial cells to activate the complete QS system, which controls the regulations of various genes that are essential for the biosynthesis of virulence factors, extracellular biopolymers (EPS) production, biofilm formation and bacterial fitness.
Part of the book: Focus on Bacterial Biofilms