Intestinal microbiota as a reservoir of extended-spectrum β-lactamase-producing Escherichia coli: An exploratory study in healthy university students

Mota, R.; Pinto, Mafalda; Palmeira, Josman Dantas; Gonçalves, Daniela; Ferreira, Helena

doi:10.1016/j.jgar.2018.05.023

Cited by 6 publications

(7 citation statements)

References 4 publications

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“…Previous antibiotic consumption and recent travel to countries with high antibiotic resistance rates have been associated with colonization, although the association with food, contact with animals and human patients, is not well known [2,11,12]. Some studies had investigated the current state of human intestinal colonization by MDR E. coli and Klebsiella pneumoniae in vulnerable populations, like the OPEN ACCESS elderly and healthcare-dependent populations, however silent carriage of MDR bacteria in human gut is still poorly studied, particularly the prevalence and intestinal colonization by these bacteria in healthy young individuals in community in Portugal [13,14].…”

Section: Introductionmentioning

confidence: 99%

“…Some studies had investigated the current state of human intestinal colonization by MDR E. coli and Klebsiella pneumoniae in vulnerable populations, like the elderly and healthcare-dependent populations, however silent carriage of MDR bacteria in human gut is still poorly studied, particularly the prevalence and intestinal colonization by these bacteria in healthy young individuals in community in Portugal [13, 14].…”

Section: Introductionmentioning

confidence: 99%

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Multidrug-resistant bacteria as intestinal colonizers and evolution of intestinal colonization in healthy university students in Portugal

Mota

Pinto

Palmeira

et al. 2021

Access Microbiology

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Multidrug-resistant bacteria have been increasingly described in healthcare institutions, however community resistance also seems to be emerging. Escherichia coli an intestinal commensal bacteria, is also a pathogen and represents an important intestinal reservoir of resistance. Our aim was the study of the intestinal colonization and of the persistence of antibiotic resistant intestinal bacteria in healthy university students of Porto, in the north of Portugal. Samples from 30 university students were collected and analysed. Two E. coli isolates were randomly obtained from each student and Gram-negative bacilli resistant to antibiotics were studied. In addition, we evaluated changes in the Gram-negative intestinal colonization of ten university students in a short period of time. Molecular characterization showed a high presence of bla TEM in commensal E. coli . Gram-negative bacteria with intrinsic and extrinsic resistance were isolated, namely Pseudomonas spp., Enterobacter spp. and Pantoea spp. We isolated three ESBL-producing E. coli from two students. These isolates showed bla CTX-M group 1 (n=1), bla CTX-M group 9 (n=2), bla TEM (n=2), bla SHV (n=1) and tetA (n=2) genes. Additionally, they showed specific virulence factors and conjugational transfer of antibiotic resistance and virulence genes. One Pseudomonas spp. isolate resistant to carbapenems was detected colonizing one student. Our results confirm that healthy young adults may be colonized with commensals showing clinically relevant antibiotic resistance mechanisms, creating a risk of silent spread of these bacteria in the community.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multidrug-resistant bacteria as intestinal colonizers and evolution of intestinal colonization in healthy university students in Portugal

Mota

Pinto

Palmeira

et al. 2021

Access Microbiology

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“…8,10 Consequently, this represents an opportunity to selectively target disease-causing bacteria without causing significant disruption to the microbiota or select for drug resistance as has been reported for broad-spectrum antibiotics such as ciprofloxacin. 28−30 Therefore, the aim of this work was to develop a small molecule antibacterial agent that is selectively active against bacteria that express β-lactamase. To do this, we employed a prodrug strategy that utilized a β-lactam cleavable motif linked to the broad-spectrum antibiotic ciprofloxacin.…”

Section: Introductionmentioning

confidence: 99%

“…Since β-lactamase enzymes are not found in mammalian cells, we hypothesized that we could exploit this enzyme as a novel antibacterial target. Furthermore, β-lactamase expression is prevalent among UTI pathogens, which can both colonize the gut and cause infection of the GU tract. , Consequently, this represents an opportunity to selectively target disease-causing bacteria without causing significant disruption to the microbiota or select for drug resistance as has been reported for broad-spectrum antibiotics such as ciprofloxacin. − Therefore, the aim of this work was to develop a small molecule antibacterial agent that is selectively active against bacteria that express β-lactamase. To do this, we employed a prodrug strategy that utilized a β-lactam cleavable motif linked to the broad-spectrum antibiotic ciprofloxacin.…”

Section: Introductionmentioning

confidence: 99%

Exploitation of Antibiotic Resistance as a Novel Drug Target: Development of a β-Lactamase-Activated Antibacterial Prodrug

Evans

Krishna

et al. 2019

J. Med. Chem.

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Expression of β-lactamase is the single most prevalent determinant of antibiotic resistance, rendering bacteria resistant to β-lactam antibiotics. In this article, we describe the development of an antibiotic prodrug that combines ciprofloxacin with a β-lactamase-cleavable motif. The prodrug is only bactericidal after activation by β-lactamase. Bactericidal activity comparable to ciprofloxacin is demonstrated against clinically relevant E. coli isolates expressing diverse β-lactamases; bactericidal activity was not observed in strains without β-lactamase. These findings demonstrate that it is possible to exploit antibiotic resistance to selectively target β-lactamase-producing bacteria using our prodrug approach, without adversely affecting bacteria that do not produce β-lactamase. This paves the way for selective targeting of drug-resistant pathogens without disrupting or selecting for resistance within the microbiota, reducing the rate of secondary infections and subsequent antibiotic use.

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“…To obtain genomic DNA, a loopful of each pure isolate culture was suspended in 300 mL of sterile distilled water and was boiled for 10 min. After 5 min of centrifugation, the supernatant was used as a DNA template for PCR amplification [17,18].…”

Section: Pcr Assaysmentioning

confidence: 99%

Conjugative plasmidic AmpC detected in Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae human clinical isolates from Portugal

et al. 2020

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AmpC is a type of β-lactamase enzyme produced by bacteria; these enzymes are classified in Class C and Group 1, and these confer resistance to cephamycin. Enterobacterales producing AmpC are reported worldwide and have great clinical importance due to therapeutic restriction and epidemiological importance once the easy dissemination by plasmidic genes to other bacteria is a real threat. These genes are naturally found in some enterobacteria as Enterobacter cloacae, Morganella morganii, and Citrobacter freundii, but other species have demonstrated similar resistance phenotype of AmpC production. Genes carried in plasmids have been described in these species conferring resistance to cefoxitin and causing therapeutic failure in some bacterial infections. This work detected and described five clinical strains of Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae that presented plasmid ampC (pAmpC) isolated from the north of Portugal collected in 2009. AmpC production was confirmed by inhibition of the enzyme by cloxacillin and boronic acid in agar diffusion tests. Also, PCR (polymerase chain reaction) was performed for the detection of gene universal to AmpC, bla ampC , and others to AmpC group: bla ACC , bla CIT , bla CMY , bla DHA , and bla EBC. The conjugation in liquid medium for 24 h was realized to determine if gene is localized in chromosome or plasmid. The isolates and their conjugants showed phenotypic characteristics and bla CMY and bla CIT were detected by PCR corroborating the AmpC characteristics observed in these bacteria. Confirmation of transfer of plasmid containing genes encoding AmpC is of high epidemiological relevance to the hospital studied and demonstrated the importance of AmpC surveillance and studies in hospital and community environments in order to choose the appropriate therapy for bacterial infections.

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Intestinal microbiota as a reservoir of extended-spectrum β-lactamase-producing Escherichia coli: An exploratory study in healthy university students

Cited by 6 publications

References 4 publications

Multidrug-resistant bacteria as intestinal colonizers and evolution of intestinal colonization in healthy university students in Portugal

Multidrug-resistant bacteria as intestinal colonizers and evolution of intestinal colonization in healthy university students in Portugal

Exploitation of Antibiotic Resistance as a Novel Drug Target: Development of a β-Lactamase-Activated Antibacterial Prodrug

Conjugative plasmidic AmpC detected in Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae human clinical isolates from Portugal

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