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Anti-Virulence Strategy against the Multidrug-Resistant Bacterial Pathogen Pseudomonas aeruginosa: Pseudolysin

Anna Clara M Galdino^1,2, Matheus P de Oliveira³, Teodorico C Ramalho⁴

¹Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Current Protein & Peptide Science

|February 8, 2019

Abstract:

Pseudomonas aeruginosa is a non-fermentative, gram-negative bacterium that is one of the most common pathogens responsible for hospital-acquired infections worldwide. The management of the infections caused by P. aeruginosa represents a huge challenge in the healthcare settings due to the increased emergence of resistant isolates, some of them resistant to all the currently available antimicrobials, which results in elevated morbimortality rates. Consequently, the development of new therapeutic strategies against multidrug-resistant P. aeruginosa is urgent and needful. P. aeruginosa is wellrecognized for its extreme genetic versatility and its ability to produce a lush variety of virulence factors. In this context, pseudolysin (or elastase B) outstands as a pivotal virulence attribute during the infectious process, playing multifunctional roles in different aspects of the pathogen-host interaction. This protein is a 33-kDa neutral zinc-dependent metallopeptidase that is the most abundant peptidase found in pseudomonal secretions, which contributes to the invasiveness of P. aeruginosa due to its ability to cleave several extracellular matrix proteins and to disrupt the basolateral intercellular junctions present in the host tissues. Moreover, pseudolysin makes P. aeruginosa able to overcome host defenses by the hydrolysis of many immunologically relevant molecules, including antibodies and complement components. The attenuation of this striking peptidase therefore emerges as an alternative and promising antivirulence strategy to combat antibiotic-refractory infections caused by P. aeruginosa. The anti-virulence approach aims to disarm the P. aeruginosa infective arsenal by inhibiting the expression/activity of bacterial virulence factors in order to reduce the invasiveness of P. aeruginosa, avoiding the emergence of resistance since the proliferation is not affected. This review summarizes the most relevant features of pseudolysin and highlights this enzyme as a promising target for the development of new anti-virulence compounds.

Insights

Pseudomonas aeruginosa infections are a growing problem due to antibiotic resistance. Targeting pseudolysin, a key virulence factor, offers a promising antivirulence strategy to combat these challenging infections.

Area of Science:

Microbiology
Pathogenesis
Drug Discovery

Background:

Pseudomonas aeruginosa is a major cause of hospital-acquired infections worldwide.
Multidrug-resistant strains pose a significant challenge, leading to high mortality rates.
Pseudolysin (elastase B) is a critical virulence factor contributing to P. aeruginosa invasiveness.

Purpose of the Study:

To review the features of pseudolysin.
To highlight pseudolysin as a potential target for novel antivirulence therapies.
To discuss the potential of antivirulence strategies against multidrug-resistant P. aeruginosa.

Main Methods:

Literature review focusing on P. aeruginosa virulence factors.
Analysis of pseudolysin's biochemical properties and role in infection.
Exploration of antivirulence strategies targeting bacterial enzymes.

Main Results:

Pseudolysin is a zinc-dependent metallopeptidase abundant in P. aeruginosa secretions.
It degrades host extracellular matrix proteins and immune molecules, facilitating infection.
Inhibiting pseudolysin can reduce bacterial invasiveness without promoting resistance.

Conclusions:

Pseudolysin is a key virulence factor of P. aeruginosa.
Targeting pseudolysin represents a promising antivirulence approach.
This strategy could be effective against antibiotic-refractory P. aeruginosa infections.

Read full analysis

Keywords:

Pseudomonas aeruginosa anti-virulence strategy bacterial pathogen pseudolysin resistance virulence.

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