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Review
. 2022 Jan 30;11(2):182.
doi: 10.3390/antibiotics11020182.

Antibiotic Discovery and Resistance: The Chase and the Race

Katia Iskandar  1   2   3 , Jayaseelan Murugaiyan  4 , Dalal Hammoudi Halat  5 , Said El Hage  6 , Vindana Chibabhai  7   8 , Saranya Adukkadukkam  4 , Christine Roques  9 , Laurent Molinier  10 , Pascale Salameh  2   6   11 , Maarten Van Dongen  12
Affiliations
Review

Antibiotic Discovery and Resistance: The Chase and the Race

Katia Iskandar et al. Antibiotics (Basel). .

Abstract

The history of antimicrobial resistance (AMR) evolution and the diversity of the environmental resistome indicate that AMR is an ancient natural phenomenon. Acquired resistance is a public health concern influenced by the anthropogenic use of antibiotics, leading to the selection of resistant genes. Data show that AMR is spreading globally at different rates, outpacing all efforts to mitigate this crisis. The search for new antibiotic classes is one of the key strategies in the fight against AMR. Since the 1980s, newly marketed antibiotics were either modifications or improvements of known molecules. The World Health Organization (WHO) describes the current pipeline as bleak, and warns about the scarcity of new leads. A quantitative and qualitative analysis of the pre-clinical and clinical pipeline indicates that few antibiotics may reach the market in a few years, predominantly not those that fit the innovative requirements to tackle the challenging spread of AMR. Diversity and innovation are the mainstays to cope with the rapid evolution of AMR. The discovery and development of antibiotics must address resistance to old and novel antibiotics. Here, we review the history and challenges of antibiotics discovery and describe different innovative new leads mechanisms expected to replenish the pipeline, while maintaining a promising possibility to shift the chase and the race between the spread of AMR, preserving antibiotic effectiveness, and meeting innovative leads requirements.

Keywords: antibiotics; antimicrobial resistance; innovative antibiotics.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Representation of a bacterial cell, illustrating the common mechanisms of antibacterial resistance. Antibiotic A corresponds to the mechanism of limiting drug uptake; B to the modification of drug target; C to antibiotic efflux; and D to drug inactivation by bacterial enzymes. Figure was prepared using Biorender.com (accessed on 20 January 2022).
Figure 2
Figure 2
The basic concepts of antibiotic resistance (the chase) and antibiotic discovery (the race) discussed in this article. Pre-clinical pipeline graph: [13]. Antibiotics in clinical development: [14]. WHO DNDi: Health Organization Drugs for Neglected Diseases Initiative; GARDP: Global Antibiotic Research and Development Partnership; SMEs: Small and Medium-Sized Enterprises; CARB-X: Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator; DRIVE-AB: Driving reinvestment in research and development for antibiotics and advocating their responsible use.
Figure 3
Figure 3
The chase and the race between antibiotics and antimicrobial resistance. The classes of antibiotics and dates of clinical introduction into the market are shown. Purple color: Synthetic antibiotics; gold color: antibiotics from other bacteria; green color: antibiotics from fungi; red color: antibiotics from actinomycetes [154].
Figure 4
Figure 4
Concise representation of some antibiotic discovery methods and new approaches to design therapies that circumvent antimicrobial resistance. Photos were prepared using Biorender.com (accessed on 20 January 2022).
See this image and copyright information in PMC

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