Engineering microbes for targeted strikes against human pathogens

Hwang, In Sung; Lee, Hui Ling; Huang, James Guoxian; Lim, Y.C.; Yew, Wen Shan; Lee, Yung Seng; Chang, Matthew Wook

doi:10.1007/s00018-018-2827-7

Cited by 15 publications

(9 citation statements)

References 105 publications

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“…The role of microbiota in regulating human health and disease status has received increasing attention in recent years. The destruction of intestinal flora has been proven to be involved in the pathogenesis of many infectious diseases [ 245 , 246 ]. Manipulating and engineering human microbiota for combatting AMR are an attractive option for POT.…”

Section: Microbiota Therapy In Combatting Amrmentioning

confidence: 99%

The Strategies of Pathogen-Oriented Therapy on Circumventing Antimicrobial Resistance

et al. 2020

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The emerging antimicrobial resistance (AMR) poses serious threats to the global public health. Conventional antibiotics have been eclipsed in combating with drug-resistant bacteria. Moreover, the developing and deploying of novel antimicrobial drugs have trudged, as few new antibiotics are being developed over time and even fewer of them can hit the market. Alternative therapeutic strategies to resolve the AMR crisis are urgently required. Pathogen-oriented therapy (POT) springs up as a promising approach in circumventing antibiotic resistance. The tactic underling POT is applying antibacterial compounds or materials directly to infected regions to treat specific bacteria species or strains with goals of improving the drug efficacy and reducing nontargeting and the development of drug resistance. This review exemplifies recent trends in the development of POTs for circumventing AMR, including the adoption of antibiotic-antibiotic conjugates, antimicrobial peptides, therapeutic monoclonal antibodies, nanotechnologies, CRISPR-Cas systems, and microbiota modulations. Employing these alternative approaches alone or in combination shows promising advantages for addressing the growing clinical embarrassment of antibiotics in fighting drug-resistant bacteria.

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Section: Microbiota Therapy In Combatting Amrmentioning

confidence: 99%

The Strategies of Pathogen-Oriented Therapy on Circumventing Antimicrobial Resistance

et al. 2020

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“…These efforts include employing members of the host microbiota to regulate the lifestyle of the pathogens for target‐specific elimination using controlled amounts of therapeutic drugs. [ 35 ] The microbiome modulation via the changes in the microbiota composition has inspired various research work to target multiple diseases such as infectious diseases, [ 36 ] cancer, [ 37 ] and metabolic syndrome. [ 38 ] In this section, we will discuss the role of microbial produced‐biochemicals used in targeting biofilm and the role of the microbiome in regulating the changes in the microbial biofilm lifestyle.…”

Section: Modulation Of Microbial Behavior To Target Microbial Biofilmmentioning

confidence: 99%

Advances in Bacterial Biofilm Management for Maintaining Microbiome Homeostasis

Liu

Hong

Yong

et al. 2020

Biotechnology Journal

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Certain microbial biofilm in the human-microbiota community can negatively impact the host microbiome. This gives rise to various methods to prevent the formation of biofilms or to facilitate biofilm dispersal from surfaces and tissues in the host. Despite all these efforts, these persistent microbial biofilms on surfaces and in the host tissue can result in health problems to the host and its microbiome. It is the adaptive behavior of microbes within the biofilm that confers on these tenacious microbes the resistance to harsh environments, antibiotic treatments, and the ability to evade the host immune system. In this review, the approaches to combat microbial biofilm in the last decade are discussed. The biochemical pathway regulating biofilm formation is first discussed, followed by the discussion of the three approaches to combat biofilm formation: physical, chemical, and biological approaches. The advances in these approaches have given rise to methods of effectively dispersing the microbial biofilm and preventing the adherence of these microbial communities altogether. As there are numerous approaches to target biofilm, in this review the attempt is to provide insights on how these approaches have been used to modulate the host-microbiome by looking at the individual strengths and weaknesses.

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“…There are already bacterial therapies in different phases of development against a wide variety of diseases, such as cancer (Duong et al , 2019 ), metabolic diseases (Isabella et al , 2018 ; Kurtz et al , 2019 ), viral infections (Lagenaur et al , 2011 ; Álvarez et al , 2015 ), and autoimmune disorders (Shigemori & Shimosato, 2017 ; Praveschotinunt et al , 2019 ). Noticeably, there are also therapeutic strains that have been programmed to destroy other bacteria (Hwang et al , 2018 ), taking advantage of the mechanisms by which bacteria compete with each other in nature (Granato et al , 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Engineering a genome‐reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo

Garrido

Piñero-Lambea

Rodríguez-Arce

et al. 2021

Molecular Systems Biology

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Bacteria present a promising delivery system for treating human diseases. Here, we engineered the genome‐reduced human lung pathogen Mycoplasma pneumoniae as a live biotherapeutic to treat biofilm‐associated bacterial infections. This strain has a unique genetic code, which hinders gene transfer to most other bacterial genera, and it lacks a cell wall, which allows it to express proteins that target peptidoglycans of pathogenic bacteria. We first determined that removal of the pathogenic factors fully attenuated the chassis strain in vivo . We then designed synthetic promoters and identified an endogenous peptide signal sequence that, when fused to heterologous proteins, promotes efficient secretion. Based on this, we equipped the chassis strain with a genetic platform designed to secrete antibiofilm and bactericidal enzymes, resulting in a strain capable of dissolving Staphylococcus aureus biofilms preformed on catheters in vitro , ex vivo , and in vivo . To our knowledge, this is the first engineered genome‐reduced bacterium that can fight against clinically relevant biofilm‐associated bacterial infections.

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Engineering microbes for targeted strikes against human pathogens

Cited by 15 publications

References 105 publications

The Strategies of Pathogen-Oriented Therapy on Circumventing Antimicrobial Resistance

The Strategies of Pathogen-Oriented Therapy on Circumventing Antimicrobial Resistance

Advances in Bacterial Biofilm Management for Maintaining Microbiome Homeostasis

Engineering a genome‐reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo

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