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. 2021 Apr 13:8:641260.
doi: 10.3389/fmed.2021.641260. eCollection 2021.

Microbial Genomics as a Catalyst for Targeted Antivirulence Therapeutics

Vitali Sintchenko  1   2   3 , Verlaine Timms  2 , Eby Sim  3 , Rebecca Rockett  1   2 , Nathan Bachmann  2 , Matthew O'Sullivan  1   2   3 , Ben Marais  1   4
Affiliations

Microbial Genomics as a Catalyst for Targeted Antivirulence Therapeutics

Vitali Sintchenko et al. Front Med (Lausanne). .

Abstract

Virulence arresting drugs (VAD) are an expanding class of antimicrobial treatment that act to "disarm" rather than kill bacteria. Despite an increasing number of VAD being registered for clinical use, uptake is hampered by the lack of methods that can identify patients who are most likely to benefit from these new agents. The application of pathogen genomics can facilitate the rational utilization of advanced therapeutics for infectious diseases. The development of genomic assessment of VAD targets is essential to support the early stages of VAD diffusion into infectious disease management. Genomic identification and characterization of VAD targets in clinical isolates can augment antimicrobial stewardship and pharmacovigilance. Personalized genomics guided use of VAD will provide crucial policy guidance to regulating agencies, assist hospitals to optimize the use of these expensive medicines and create market opportunities for biotech companies and diagnostic laboratories.

Keywords: antibacterial treatment; antimicrobial stewardship; genome sequence analysis; surveillance; virulence.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overview of the competitive landscape for virulence arresting drugs (VAD).
Figure 2
Figure 2
Examples of variation in virulence genes and proteins affecting VAD targets. The size of letters representing nucleotides (DNA) or amino acids (Protein) reflects their relative frequency in individual positions in the VAD target gene. Only 6% of Streptococcus pneumoniae comB gene (75-bp of 1,326-bp gene) and 2% of Clostridium difficile tcdB gene (90-bp of 7,101-bp gene) are shown; multiple sequence variations with amino acid relevance are present. Amino acids are colored according to their chemical properties: polar amino acids are green, basic blue, and hydrophobic are black. The height of the y-axis indicates the maximum entropy for the given sequence type. Prepared using Weblogo (www.weblogo.berkeley.edu).
Figure 3
Figure 3
Proposed pathway for using genomic profiling for VAD selection.
See this image and copyright information in PMC

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