Search results for "Antivirulence"

Anti-adhesion agents against Gram-positive pathogens

2014

The rise of antibiotic-resistance as well as the deficiency of investments by pharmaceutical companies in the development of new antibiotics, have stimulated the investigation of alternative strategies to conventional antibiotics for counteracting the pathogens. A fundamental step of Gram positive pathogenesis is the bacterial adhesion to the host tissue involving a direct and a specific interaction between bacterial surface molecules and host ligands. Targeting the adhesion is a good strategy to design novel anti-infective drugs agents useful to interfere with the pathogenic process and with a virulence mechanism as biofilm formation. This review is focused on anti-virulence compounds whic…

Targeting Bacterial Sortase A with Covalent Inhibitors: 27 New Starting Points for Structure-Based Hit-to-Lead Optimization.

2019

Because of its essential role as a bacterial virulence factor, enzyme sortase A (SrtA) has become an attractive target for the development of new antivirulence drugs against Gram-positive infections. Here we describe 27 compounds identified as covalent inhibitors of

Novel strategies in the war against antibiotic resistance

2021

The global threat of antibiotic resistance is steadily growing. Antibiotic resistancemay involve any class of antibiotic, including second- and third-line agents that have been considered to date the last-resort drugs to counteract common infections. We may lose our capability to keep under control many common bacterial infections [1]. Despite this, in the past decade significant research efforts have been made to develop new antibacterial strategies able to treat multidrug-resistant infections; however, no new therapeutic approach has yet reached the clinic [2,3]. In order to identify new valuable antimicrobial drugs, it is important to consider the main bacterial resistance mechanisms in …

Targeting the Sortase A Transpeptidase to Tackle Gram-positive Pathogens

2013

The virulence factors include the cell-wall associated proteins called MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) that can promote the adhesion to host proteins, for example, the fibronectin that is very common in host tissues. The cellwall associated proteins are necessary for host colonization, invasion, immune evasion and biofilm formation [4]. The biofilms, multistratified bacterial communities that grow on a biological or artificial surface, are responsible for chronic infectious diseases and for device or biomaterial associated infections, and are more resistant to host immune defence system and to conventional antibiotics [5].

Inhibitors of antibiotic resistance mechanisms: clinical applications and future perspectives

2020

Bacterial strains responsible for antibiotic resistant infections are increasing in an alarming way and the evolution of resistance mechanisms seems to be unstoppable. In the past decade, many efforts have been made in order to counteract this phenomenon but very few compounds have reached clinical trials. The development of new classes of antibiotics able to overcome the main bacterial drug resistance mechanisms is urgently required to counter the imminent danger of a postantibiotic era.

Therapeutic Strategies To Counteract Antibiotic Resistance in MRSA Biofilm‐Associated Infections

2021

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as one of the leading causes of persistent human infections. This pathogen is widespread and is able to colonize asymptomatically about a third of the population, causing moderate to severe infections. It is currently considered the most common cause of nosocomial infections and one of the main causes of death in hospitalized patients. Due to its high morbidity and mortality rate and its ability to resist most antibiotics on the market, it has been termed a “superbug”. Its ability to form biofilms on biotic and abiotic surfaces seems to be the primarily means of MRSA antibiotic resistance and pervasiveness. Importantly, more tha…

Sortase A: An ideal target for anti-virulence drug development

2014

Sortase A is a membrane enzyme responsible for the anchoring of surface-exposed proteins to the cell wall envelope of Gram-positive bacteria. As a well-studied member of the sortase subfamily catalysing the cell wall anchoring of important virulence factors to the surface of staphylococci, enterococci and streptococci, sortase A plays a critical role in Gram-positive bacterial pathogenesis. It is thus considered a promising target for the development of new anti-infective drugs that aim to interfere with important Gram-positive virulence mechanisms, such as adhesion to host tissues, evasion of host defences, and bio fi lm formation. The additional properties of sortase A as an enzyme that i…

The Future of Antibiotic: From the Magic Bullet to the Smart Bullet

2014

Bacterial Biofilm Inhibition in the Development of Effective Anti-Virulence Strategy

2018

There is an urgent need for new therapeutic strategies to counteract the global threat of antibiotic resistance, which has become, in recent years, one of the major public health concern. An important contribution to the microbial survival in hostile environments has been given by the capability of pathogens to form sessile communities able to adhere to biotic or abiotic surfaces, known as biofilms.

A new class of phenylhydrazinylidene derivatives as inhibitors of Staphylococcus aureus biofilm formation

2016

In the struggle against the emergence of the antibiotic resistance, new molecules targeting biofilm formation could be useful as adjuvant of conventional antibiotics. This study focused on a new class of 2-phenylhydrazinylidene derivatives as antivirulence agents. The compound 12e showed interesting activities against biofilm formation of all tested Staphylococcus aureus strains with IC50 ranging from 1.7 to 43 µM; compounds 12f and 13a resulted strong inhibitors of S. aureus ATCC 6538 and ATCC 29213 biofilm formation with IC50 of 0.9 and 0.8 µM, respectively. A preliminary study on the mechanism of action was carried on evaluating the inhibition of sortase A transpeptidase. Compound 12e re…