Engineering commensal bacteria for prophylaxis against infection

Abstract

Infectious diseases are the leading causes of death worldwide. The development of efficient and low cost prophylactics to prevent pathogenic infection is given high priority in the twenty-first century. Commensal bacteria are largely seen as harmless and can survive symbiotically (in many cases) in niches throughout the human body. Advances in genetic engineering and understanding of pathogenesis have revealed many potential strategies to develop engineered bacteria for prophylaxis purposes: including live vaccines and anti-infective agents. In this review we discuss recent advances and potentialities of prophylaxis with engineered bacteria.

Engineered bacteria as therapeutic agents

“…Intervention against viral and bacterial infections has been addressed with engineered bacteria, which have been recently reviewed [49]. A wide variety of approaches have been followed, including binding of toxins, interference with quorum sensing molecules and adhesion mechanisms, release of neutralizing antibodies and antimicrobial factors, which are summarized in Figure 3.…”

Sustainable therapies by engineered bacteria

“…Engineered bacteria can also help in these objectives. Different strategies have been investigated against infectious diseases, including toxin neutralization, blocking pathogen adhesion or interfering with quorum sensing (QS) signals (Goh et al ., 2012; Hwang et al ., 2016). There are examples of engineered strains against major diarrhoeal diseases, including bacteria such as Vibrio cholera (Duan and March, 2010) and viruses like rotaviruses, a major cause of severe diarrhoea in children under 5 years (Pant et al ., 2006; Álvarez et al ., 2015).…”

Synthetic biology platform technologies for antimicrobial applications

“…In later iterations, non-pathogenic microbes were modified to display toxin receptor-mimics that act as competitive inhibitors of pathogenic toxins [84][85][86]. Other approaches used engineered probiotics to disrupt pathogen quorum sensing and prevent virulent gene expression, demonstrating a generalizable method of interfering with pathogen communication for antimicrobial purposes [87,88]. Additional advancements in probiotic-based therapeutics focused on promoting long-term viability of recombinant bacteria by engineering commensal species that would be expected to stably colonize the mammalian host [87].…”

“…Other approaches used engineered probiotics to disrupt pathogen quorum sensing and prevent virulent gene expression, demonstrating a generalizable method of interfering with pathogen communication for antimicrobial purposes [87,88]. Additional advancements in probiotic-based therapeutics focused on promoting long-term viability of recombinant bacteria by engineering commensal species that would be expected to stably colonize the mammalian host [87]. Prophylactics for human immunodeficiency virus (HIV) were developed using this approach, by modifying Lactobacillus and Escherichia Coli (E. coli) species that naturally colonize the cervicovaginal tract to secrete antiviral peptides [89][90][91].…”