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Open AccessReview

Overcoming Intrinsic and Acquired Resistance Mechanisms Associated with the Cell Wall of Gram-Negative Bacteria

1
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
2
National Infection Service, Research and Development Institute, Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK
*
Author to whom correspondence should be addressed.
R.E.I. and D.A.H. are joint first authors.
Received: 2 September 2020 / Revised: 16 September 2020 / Accepted: 17 September 2020 / Published: 19 September 2020
(This article belongs to the Special Issue Novel Targets and Mechanisms in Antimicrobial Drug Discovery)
The global increase in multi-drug-resistant bacteria is severely impacting our ability to effectively treat common infections. For Gram-negative bacteria, their intrinsic and acquired resistance mechanisms are heightened by their unique cell wall structure. The cell wall, while being a target of some antibiotics, represents a barrier due to the inability of most antibacterial compounds to traverse and reach their intended target. This means that its composition and resulting mechanisms of resistance must be considered when developing new therapies. Here, we discuss potential antibiotic targets within the most well-characterised resistance mechanisms associated with the cell wall in Gram-negative bacteria, including the outer membrane structure, porins and efflux pumps. We also provide a timely update on the current progress of inhibitor development in these areas. Such compounds could represent new avenues for drug discovery as well as adjuvant therapy to help us overcome antibiotic resistance. View Full-Text
Keywords: antibiotic discovery; antimicrobial resistance; cell wall; Gram-negative bacteria antibiotic discovery; antimicrobial resistance; cell wall; Gram-negative bacteria
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MDPI and ACS Style

Impey, R.E.; Hawkins, D.A.; Sutton, J.M.; Soares da Costa, T.P. Overcoming Intrinsic and Acquired Resistance Mechanisms Associated with the Cell Wall of Gram-Negative Bacteria. Antibiotics 2020, 9, 623. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9090623

AMA Style

Impey RE, Hawkins DA, Sutton JM, Soares da Costa TP. Overcoming Intrinsic and Acquired Resistance Mechanisms Associated with the Cell Wall of Gram-Negative Bacteria. Antibiotics. 2020; 9(9):623. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9090623

Chicago/Turabian Style

Impey, Rachael E.; Hawkins, Daniel A.; Sutton, J. M.; Soares da Costa, Tatiana P. 2020. "Overcoming Intrinsic and Acquired Resistance Mechanisms Associated with the Cell Wall of Gram-Negative Bacteria" Antibiotics 9, no. 9: 623. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9090623

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