Innovative Solutions to Sticky Situations: Antiadhesive Strategies for Treating Bacterial Infections

Abstract

Bacterial adherence to host tissue is an essential process in pathogenesis, necessary for invasion and colonization and often required for the efficient delivery of toxins and other bacterial effectors. As existing treatment options for common bacterial infections dwindle, we find ourselves rapidly approaching a tipping point in our confrontation with antibiotic-resistant strains and in desperate need of new treatment options. Bacterial strains defective in adherence are typically avirulent and unable to cause infection in animal models. The importance of this initial binding event in the pathogenic cascade highlights its potential as a novel therapeutic target. This article seeks to highlight a variety of strategies being employed to treat and prevent infection by targeting the mechanisms of bacterial adhesion. Advancements in this area include the development of novel antivirulence therapies using small molecules, vaccines, and peptides to target a variety of bacterial infections. These therapies target bacterial adhesion through a number of mechanisms, including inhibition of pathogen receptor biogenesis, competition-based strategies with receptor and adhesin analogs, and the inhibition of binding through neutralizing antibodies. While this article is not an exhaustive description of every advancement in the field, we hope it will highlight several promising examples of the therapeutic potential of antiadhesive strategies.

Essential Oils Biofilm Modulation Activity, Chemical and Machine Learning Analysis—Application on Staphylococcus aureus Isolates from Cystic Fibrosis Patients

“…A negative modulation or a complete inhibition of biofilm formation may represent an important strategy for infection control and might be considered as a major target for the development of novel therapeutic agents [8]. Hence, there is a need to develop innovative approaches that lower or block biofilm formation without affecting bacterial vitality, avoiding the appearance of escape mutants [9,10]. The use of anti-biofilm compounds could enhance the effectiveness of conventional therapies [11,12], particularly in chronic infections; this could represent a suitable approach to treat CF patients' infections.…”

Nonribosomal antibacterial peptides isolated from Streptomyces agglomeratus 5-1-3 in the Qinghai-Tibet Plateau

“…Since the first report of MRSA by Jevons in 1961, MRSA has become a common pathogenic bacterium in clinical practice, especially in postoperative infections. It is also a common superbacterium, greatly challenging clinical treatment [ 1 ]. MRSA bacteria expressed a variety of antibiotic resistance-related genes and exhibited different degrees of resistance to β -lactam, quinolone, aminoglycoside, tetracycline, and macrolide antibiotics.…”

“…Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common pathogenic bacteria in hospital and community infections [ 1 , 2 ]. MRSA exhibits stronger infectivity than the Gram-positive cocci in any part of the human body, and the rate of infection incidence rises continuously [ 3 ].…”

Targeted Anti-Biofilm Therapy: Dissecting Targets in the Biofilm Life Cycle

“…Developing adhesion targeting compounds has been a long and in-depth development process. Thus, some scholars have proposed a strategy to interfere with adhesin, which uses compounds as analogues of bacterial adhesin receptors to make bacteria “mistakenly” adhere to the host to achieve anti-adhesion effects [ 79 , 80 ]. A treatment scheme using α-mannoside that interferes with FimH1 for treatment of catheter-related urinary tract infection (CAUTI) was applied [ 81 , 82 ].…”