CRISPR/Cas9-Mediated Re-Sensitization of Antibiotic-Resistant Escherichia coli Harboring Extended-Spectrum ��-Lactamases

Kim, Jun‐Seob; Cho, Da Hyeong; Park, Myeong Seo; Chung, Woo Jae; Shin, Dong Woo; Ko, Kwan Soo; Kweon, Dae Hyuk

doi:10.4014/jmb.1508.08080

Cited by 106 publications

(91 citation statements)

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“…For these reasons, among others, it is crucial that we begin to develop new treatments to combat bacterial infection. Researchers have already begun investigating potential new antimicrobial strategies (22), such as the use of antimicrobial peptides (23, 24), phage therapy (25, 26), and gene-editing enzymes (27, 28). Here, we report another promising novel approach: the use of predatory bacteria to control Gram-negative human pathogens.…”

Section: Discussionmentioning

confidence: 99%

Predatory Bacteria Attenuate Klebsiella pneumoniae Burden in Rat Lungs

Shatzkes

Singleton

Tang

et al. 2016

mBio

104

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Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus are predatory bacteria that naturally—and obligately—prey on other Gram-negative bacteria, and their use has been proposed as a potential new approach to control microbial infection. The ability of predatory bacteria to prey on Gram-negative human pathogens in vitro is well documented; however, the in vivo safety and efficacy of predatory bacteria have yet to be fully assessed. In this study, we examined whether predatory bacteria can reduce bacterial burden in the lungs in an in vivo mammalian system. Initial safety studies were performed by intranasal inoculation of rats with predatory bacteria. No adverse effects or lung pathology were observed in rats exposed to high concentrations of predatory bacteria at up to 10 days postinoculation. Enzyme-linked immunosorbent assay (ELISA) of the immune response revealed a slight increase in inflammatory cytokine levels at 1 h postinoculation that was not sustained by 48 h. Additionally, dissemination experiments showed that predators were efficiently cleared from the host by 10 days postinoculation. To measure the ability of predatory bacteria to reduce microbial burden in vivo, we introduced sublethal concentrations of Klebsiella pneumoniae into the lungs of rats via intranasal inoculation and followed with multiple doses of predatory bacteria over 24 h. Predatory bacteria were able to reduce K. pneumoniae bacterial burden, on average, by more than 3.0 log10 in the lungs of most rats as measured by CFU plating. The work presented here provides further support for the idea of developing predatory bacteria as a novel biocontrol agent.

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Section: Discussionmentioning

confidence: 99%

Predatory Bacteria Attenuate Klebsiella pneumoniae Burden in Rat Lungs

Shatzkes

Singleton

Tang

et al. 2016

mBio

104

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“…61 In addition, owing to the delivery system that acts in higher organisms, RNA-guided nucleases could enable us to modulate the prevalence of specific genes such as antibiotic resistance genes and virulence determinants in wild-type populations. 87 The Cas9 nuclease targeting specific DNA sequences of bacterial pathogens and antibiotic resistance gene are delivered to microbial populations using polymer-derivatized CRISPR nanocomplexes, 36 bacteria carrying plasmids transmissible by conjugation, 61,88 and/or bacteriophages 60,61 (Figure 2). Gomma et al 62 used the typed I-E CRISPR-Cas system of E. coli, encoding six cas genes in two operons including casABCDE and cas3, 53 to specific and essential sequences in the genomes of different sequences.…”

Section: Crispr-cas System Neutralizing Antibiotic-resistant Genesmentioning

confidence: 99%

<p>How CRISPR-Cas System Could Be Used to Combat Antimicrobial Resistance</p>

Gholizadeh¹,

Köse²,

Dao³

et al. 2020

IDR

109

101

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Rapid emergence of antibiotic-resistant bacteria has made it harder for us to combat infectious diseases and to develop new antibiotics. The clustered regularly interspaced short palindromic repeats-CRISPR-associated (CRISPR-Cas) system, as a bacterial adaptive immune system, is recognized as one of the new strategies for controlling antibioticresistant strains. The programmable Cas nuclease of this system used against bacterial genomic sequences could be lethal or could help reduce resistance of bacteria to antibiotics. Therefore, this study aims to review using the CRISPR-Cas system to promote sensitizing bacteria to antibiotics. We envision that CRISPR-Cas approaches may open novel ways for the development of smart antibiotics, which could eliminate multidrug-resistant (MDR) pathogens and differentiate between beneficial and pathogenic microorganisms. These systems can be exploited to quantitatively and selectively eliminate individual bacterial strains based on a sequence-specific manner, creating opportunities in the treatment of MDR infections, the study of microbial consortia, and the control of industrial fermentation.

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“…Following challenge with lytic phages, drug-resistant bacteria were eliminated, thus enriching for antibiotic-sensitive bacteria. Similarly, Kim et al used a CRISPR-Cas9based strategy termed resensitization to antibiotics from resistance (ReSAFR) to restore ␤-lactam antibiotic activity in ESBL-producing E. coli (49). The authors targeted separate conserved sequences among multiple TEM-and SHV-type ESBL E. coli strains.…”

Section: Infectious Disease Applicationsmentioning

confidence: 99%

CRISPR-Cas Biology and Its Application to Infectious Diseases

2019

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Infectious diseases remain a global threat contributing to excess morbidity and death annually, with the persistent potential for destabilizing pandemics. Improved understanding of the pathogenesis of bacteria, viruses, fungi, and parasites, along with rapid diagnosis and treatment of human infections, is essential for improving infectious disease outcomes worldwide. Genomic loci in bacteria and archaea, termed clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins, function as an adaptive immune system for prokaryotes, protecting them against foreign invaders. CRISPR-Cas9 technology is now routinely applied for efficient gene editing, contributing to advances in biomedical science. In the past decade, improved understanding of other diverse CRISPR-Cas systems has expanded CRISPR applications, including in the field of infectious diseases. In this review, we summarize the biology of CRISPR-Cas systems and discuss existing and emerging applications to evaluate mechanisms of host-pathogen interactions, to develop accurate and portable diagnostic tests, and to advance the prevention and treatment of infectious diseases.

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CRISPR/Cas9-Mediated Re-Sensitization of Antibiotic-Resistant Escherichia coli Harboring Extended-Spectrum ��-Lactamases

Cited by 106 publications

References 0 publications

Predatory Bacteria Attenuate Klebsiella pneumoniae Burden in Rat Lungs

Predatory Bacteria Attenuate Klebsiella pneumoniae Burden in Rat Lungs

<p>How CRISPR-Cas System Could Be Used to Combat Antimicrobial Resistance</p>

CRISPR-Cas Biology and Its Application to Infectious Diseases

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