Monoclonal Antibodies as an Antibacterial Approach Against Bacterial Pathogens

In the beginning of the 21st century, the frequency of antimicrobial resistance (AMR) has reached an apex, where even 4th and 5th generation antibiotics are becoming useless in clinical settings. In turn, patients are suffering from once-curable infections, with increases in morbidity and mortality....

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Main Authors: Daniel V. Zurawski, Molly K. McLendon
Format: Article
Language:English
Published: MDPI AG 2020-04-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/9/4/155
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spelling doaj-2ed8174681cd40bd9eb3a77112d6424c2020-11-25T03:01:07ZengMDPI AGAntibiotics2079-63822020-04-01915515510.3390/antibiotics9040155Monoclonal Antibodies as an Antibacterial Approach Against Bacterial PathogensDaniel V. Zurawski0Molly K. McLendon1Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAWound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAIn the beginning of the 21st century, the frequency of antimicrobial resistance (AMR) has reached an apex, where even 4th and 5th generation antibiotics are becoming useless in clinical settings. In turn, patients are suffering from once-curable infections, with increases in morbidity and mortality. The root cause of many of these infections are the ESKAPEE pathogens (<i>Enterococcus</i> species, <i>Staphylococcus aureus</i>, <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, <i>Pseudomonas aeruginosa</i>, <i>Enterobacter</i> species, and <i>Escherichia coli</i>), which thrive in the nosocomial environment and are the bacterial species that have seen the largest rise in the acquisition of antibiotic resistance genes. While traditional small-molecule development still dominates the antibacterial landscape for solutions to AMR, some researchers are now turning to biological approaches as potential game changers. Monoclonal antibodies (mAbs)—more specifically, human monoclonal antibodies (Hu-mAbs)—have been highly pursued in the anti-cancer, autoimmune, and antiviral fields with many success stories, but antibody development for bacterial infection is still just scratching the surface. The untapped potential for Hu-mAbs to be used as a prophylactic or therapeutic treatment for bacterial infection is exciting, as these biologics do not have the same toxicity hurdles of small molecules, could have less resistance as they often target virulence proteins rather than proteins required for survival, and are narrow spectrum (targeting just one pathogenic species), therefore avoiding the disruption of the microbiome. This mini-review will highlight the current antibacterial mAbs approved for patient use, the success stories for mAb development, and new Hu-mAb products in the antibacterial pipeline.https://www.mdpi.com/2079-6382/9/4/155antibodiesESKAPE pathogens<i>Escherichia coli</i>antibacterialtherapeuticclinical trial
collection DOAJ
language English
format Article
sources DOAJ
author Daniel V. Zurawski
Molly K. McLendon
spellingShingle Daniel V. Zurawski
Molly K. McLendon
Monoclonal Antibodies as an Antibacterial Approach Against Bacterial Pathogens
Antibiotics
antibodies
ESKAPE pathogens
<i>Escherichia coli</i>
antibacterial
therapeutic
clinical trial
author_facet Daniel V. Zurawski
Molly K. McLendon
author_sort Daniel V. Zurawski
title Monoclonal Antibodies as an Antibacterial Approach Against Bacterial Pathogens
title_short Monoclonal Antibodies as an Antibacterial Approach Against Bacterial Pathogens
title_full Monoclonal Antibodies as an Antibacterial Approach Against Bacterial Pathogens
title_fullStr Monoclonal Antibodies as an Antibacterial Approach Against Bacterial Pathogens
title_full_unstemmed Monoclonal Antibodies as an Antibacterial Approach Against Bacterial Pathogens
title_sort monoclonal antibodies as an antibacterial approach against bacterial pathogens
publisher MDPI AG
series Antibiotics
issn 2079-6382
publishDate 2020-04-01
description In the beginning of the 21st century, the frequency of antimicrobial resistance (AMR) has reached an apex, where even 4th and 5th generation antibiotics are becoming useless in clinical settings. In turn, patients are suffering from once-curable infections, with increases in morbidity and mortality. The root cause of many of these infections are the ESKAPEE pathogens (<i>Enterococcus</i> species, <i>Staphylococcus aureus</i>, <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, <i>Pseudomonas aeruginosa</i>, <i>Enterobacter</i> species, and <i>Escherichia coli</i>), which thrive in the nosocomial environment and are the bacterial species that have seen the largest rise in the acquisition of antibiotic resistance genes. While traditional small-molecule development still dominates the antibacterial landscape for solutions to AMR, some researchers are now turning to biological approaches as potential game changers. Monoclonal antibodies (mAbs)—more specifically, human monoclonal antibodies (Hu-mAbs)—have been highly pursued in the anti-cancer, autoimmune, and antiviral fields with many success stories, but antibody development for bacterial infection is still just scratching the surface. The untapped potential for Hu-mAbs to be used as a prophylactic or therapeutic treatment for bacterial infection is exciting, as these biologics do not have the same toxicity hurdles of small molecules, could have less resistance as they often target virulence proteins rather than proteins required for survival, and are narrow spectrum (targeting just one pathogenic species), therefore avoiding the disruption of the microbiome. This mini-review will highlight the current antibacterial mAbs approved for patient use, the success stories for mAb development, and new Hu-mAb products in the antibacterial pipeline.
topic antibodies
ESKAPE pathogens
<i>Escherichia coli</i>
antibacterial
therapeutic
clinical trial
url https://www.mdpi.com/2079-6382/9/4/155
work_keys_str_mv AT danielvzurawski monoclonalantibodiesasanantibacterialapproachagainstbacterialpathogens
AT mollykmclendon monoclonalantibodiesasanantibacterialapproachagainstbacterialpathogens
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