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Review
. 2022 Mar 28;15(4):413.
doi: 10.3390/ph15040413.

Progress Report: Antimicrobial Drug Discovery in the Resistance Era

Pottathil Shinu  1 , Abdulaziz K Al Mouslem  2 , Anroop B Nair  2 , Katharigatta N Venugopala  2   3 , Mahesh Attimarad  2 , Varsha A Singh  4 , Sreeharsha Nagaraja  2   5 , Ghallab Alotaibi  6 , Pran Kishore Deb  7
Affiliations
Review

Progress Report: Antimicrobial Drug Discovery in the Resistance Era

Pottathil Shinu et al. Pharmaceuticals (Basel). .

Abstract

Antibiotic resistance continues to be a most serious threat to public health. This situation demands that the scientific community increase their efforts for the discovery of alternative strategies to circumvent the problems associated with conventional small molecule therapeutics. The Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report (published in June 2021) discloses the rapidly increasing number of bacterial infections that are mainly caused by antimicrobial-resistant bacteria. These concerns have initiated various government agencies and other organizations to educate the public regarding the appropriate use of antibiotics. This review discusses a brief highlight on the timeline of antimicrobial drug discovery with a special emphasis on the historical development of antimicrobial resistance. In addition, new antimicrobial targets and approaches, recent developments in drug screening, design, and delivery were covered. This review also discusses the emergence and roles of various antibiotic adjuvants and combination therapies while shedding light on current challenges and future perspectives. Overall, the emergence of resistant microbial strains has challenged drug discovery but their efforts to develop alternative technologies such as nanomaterials seem to be promising for the future.

Keywords: MDR; adjuvants; antimicrobial resistance; antimicrobial targets; drug discovery; drug screening; drug targets.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Pie chart showing current number of antimicrobial-resistant mediated global deaths and expected number of global deaths due to antimicrobial-resistant infectious diseases in 2050.
Figure 2
Figure 2
The number of research publications in antimicrobial resistance from 2000 to 2021.
Figure 3
Figure 3
Schematic representation of historical aspects for the development of antimicrobial resistance.
Figure 4
Figure 4
An illustration representing the mode of action of carbon nanodots against bacterial cells. (A) Adhesion of carbon nanodots to the bacterial cell surface, and the visible-light-induced ROS generation. (B) ROS mediated intracellular bacterial cell damage.
Figure 5
Figure 5
A schematic illustration of stimuli-responsive nanomaterials for different applications including therapy, bio-imaging as well as triggered drug release (Reprinted from ref. [144]).
Figure 6
Figure 6
A schematic representation of the different mechanisms of action of antibiotic adjuvants. (A) Inhibition of hydrolase/modifying enzyme either on antibiotics as shown in (1) or the antibiotic targets as shown in (2); (B) enhancement of the intracellular accumulation of the antibiotic by the inhibition of efflux pumps as shown in (1), the facilitation of the antibiotic through the surface membrane as shown in (2) or the destruction of the biofilm as shown in (3); (C) the complementary mechanism; (D) inhibiting the signaling and regulatory pathway responsible for mediating the antibiotic resistance; (E) the enhancement of the host defense through the stimulation of the immune cells.
Figure 7
Figure 7
Chemical structures of antimicrobial agents.
Figure 7
Figure 7
Chemical structures of antimicrobial agents.
Figure 7
Figure 7
Chemical structures of antimicrobial agents.
Figure 7
Figure 7
Chemical structures of antimicrobial agents.
Figure 7
Figure 7
Chemical structures of antimicrobial agents.
Figure 7
Figure 7
Chemical structures of antimicrobial agents.
See this image and copyright information in PMC

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