Abstract
Antimicrobial resistance (AMR) is a concerning global threat that, if not addressed, could lead to increases in morbidity and mortality, coupled with societal and financial burdens. The emergence of AMR bacteria can be attributed, in part, to the decreased development of new antibiotics, increased misuse and overuse of existing antibiotics, and inadequate treatment options for biofilms formed during bacterial infections. Biofilms are complex microbiomes enshrouded in a self-produced extracellular polymeric substance (EPS) that is a primary defense mechanism of the resident microorganisms against antimicrobial agents and the host immune system. In addition to the physical protective EPS barrier, biofilm-resident bacteria exhibit tolerance mechanisms enabling persistence and the establishment of recurrent infections. As current antibiotics and therapeutics are becoming less effective in combating AMR, new innovative technologies are needed to address the growing AMR threat. This perspective article highlights such a product, CMTX-101, a humanized monoclonal antibody that targets a universal component of bacterial biofilms, leading to pathogen-agnostic rapid biofilm collapse and engaging three modes of action—the sensitization of bacteria to antibiotics, host immune enablement, and the suppression of site-specific tissue inflammation. CMTX-101 is a new tool used to enhance the effectiveness of existing, relatively inexpensive first-line antibiotics to fight infections while promoting antimicrobial stewardship.
Highlights
Antibiotics revolutionized the global healthcare industry by ushering in an era of significantly lower morbidity and mortality associated with lethal bacterial infections
integration host factor (IHF) and HU generally have a conserved amino acid sequence homology in the DNA-binding region, and perhaps more importantly, a highly conserved three-dimensional conformation that enables the DNABII proteins to bind with high affinity to the pre-bent Holliday junction-like structures that exist in the extracellular DNA (eDNA) lattice of bacterial biofilms [41,42]
Infections attributed to bacterial biofilms can be separated into device- and tissueassociated infections [63]; examples of device-associated biofilm infections include infections associated with neurosurgical implants, orthopedic implants, artificial heart valves, pacemakers, and vascular catheters, while tissue-associated biofilm infections can include chronic urinary tract infections, chronic wound infections, ventilator-associated pneumonia, chronic rhinosinusitis, osteomyelitis, otitis media, and periodontitis
Summary
Antibiotics revolutionized the global healthcare industry by ushering in an era of significantly lower morbidity and mortality associated with lethal bacterial infections. According to the Centers for Disease Control and Prevention (CDC), the United States has more than 2.8 million antibiotic-resistant infections annually, leading to more than 35,000 deaths; the misuse and overuse of antimicrobial agents are the two main drivers of the development of AMR bacteria [3]. A compounding factor in the increasing prevalence of AMR bacteria is that the discovery and development of new antibiotic classes have been essentially stagnant for decades, which has limited the options for physicians to treat AMR bacterial infections. This article highlights the development of one such novel nontraditional product, CMTX-101, an anti-DNABII humanized monoclonal antibody being developed by Clarametyx Biosciences, Inc. CMTX-101 targets a universal component of bacterial biofilms and causes rapid and pathogen-agnostic biofilm collapse, enhancing the effectiveness of innate immune effectors and killing by antibacterial agents, enabling existing, relatively inexpensive first-line antibiotics to fight infections better
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