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Dynamics and Molecular Features of Multidrug-Resistant Enterobacterales Lineages in Global...
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Dynamics and Molecular Features of Multidrug-Resistant Enterobacterales Lineages in Global Dissemination in a One Health Context (Humans, Animals, and Environment)

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 22204

Special Issue Editors

Dr. Raspail Carrel Founou Zangue

E-Mail Website
Guest Editor
Microbiology-Hematology and Immunology, University of Dschang, Dschang, Cameroon
Interests: AMR; Food safety; One health approach
Dr. Malik Aydin

E-Mail Website
Guest Editor
Center of Pediatrics, Helios University Hospital Wuppertal, Wuppertal, Germany
Interests: immunology and infectious diseases in pediatrics; proteomics in asthmatic children

Special Issue Information

Dear Colleagues,

The aim of this Special Issue is to elucidate the molecular features of genes, plasmids, and clones of Enteroacterales in low- and middle-income nations with their limited resources for molecular analysis of the clonality of the Enterobacterales species and molecular characterization of the bacterial antimicrobial resistances.

Among multidrug-resistant (MDR) bacteria, Gram-negative bacilli (GNB) are a most pressing concern. The Enterobacterales is a huge family of pathogens involved in community-associated and nosocomial infections. Due to the emergence and spread of multidrug-resistant (MDR) Enterobacterales in healthcare settings, carbapenems have become one of the last-resort antimicrobials for severe infections caused by these MDR-GNB isolates. Moreover, there are different issues with the different species that we see causing antibiotic resistance, e.g., E. coli, Klebsiella spp.

Extended-spectrum beta-lactamase producing GNB (ESBL) are intrinsically resistant to oxyimino-beta-lactams, including the first three generations of cephalosporins and some beta-lactam/beta-lactamase inhibitor combinations and aztreonam. ESBL-producing GNB should be considered when patients have been pretreated with oxyimino-betalactams, especially third-generation cephalosporins. Urine catheter users have an additional risk. The ESBL rate up to >80% is not only high in Southern and Western Europe, in most Asian countries, in the Middle East Region, and in South America, but also in numerous African regions. The travel history is therefore important since such pathogens will last for weeks after returning from these regions. The high risk to all MDR-GNB must be taken into account in the continuous migration situation. Carbapenems work well against these infections. However, they are essentially the broadest spectrum class of antimicrobials that we have. Moreover, overusing these leads to resistance in Enterobacterales, causing the problem that we have very few options remaining for carbapenem-resistant bacteria, which are rising in numbers worldwide. A question that often comes up is, how do we treat infections associated with such MDR Enterobacterales? Furthermore, MDR-GNB are considered a cross-sectoral issue because the extensive use of antimicrobial agents in livestock has led to emergence of MDR-GNB that can spread directly to exposed workers or indirectly through the food chain. Therefore, surveillance of livestock-associated MDR-GNB, their resistance, and virulence determinants are important for conducting epidemiological analysis of such factors, designing risk management, and strategically controlling farming due to the fact that these data are highly relevant to public health.

As Guest Editor of this Special Issue, I am delighted to invite colleagues investigating any of the pathogenic Enterobacterales within the areas of their ecology, genetics, genomics, immunology, diagnostic detection, public health, and antimicrobial development to submit their manuscripts to this Special Issue in the form of original research, short communication, and reviews. This includes original clinical and laboratory-based research, together with reports of clinical trials and reviews dealing with the epidemiology, clinical diagnosis, treatment, and control of MDR-GNB, including ESBL and CRE.

Dr. Raspail Carrel Founou Zangue
Dr. Malik Aydin
Guest Editors

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Keywords

  • enterobacterales
  • ESBL
  • CRE
  • molecular epidemiology
  • clonality
  • livestock
  • environment
  • diagnostic tools
  • therapy options
  • low-resource nations

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Published Papers (7 papers)

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Research

10 pages, 1078 KiB  
Article
Beta-Lactam-Resistant Enterobacterales Isolated from Landfill Leachates
by Alejandra Mondragón-Quiguanas, Miguel Ángel Villaquirán-Muriel, Sandra Patricia Rivera, Doris Rosero-García, Carlos Aranaga, Adriana Correa and Aura Falco
Pathogens 2022, 11(10), 1077; https://doi.org/10.3390/pathogens11101077 - 22 Sep 2022
Cited by 1 | Viewed by 2019
Abstract
Antibiotic resistance is one of the main challenges worldwide due to the high morbidity and mortality caused by infections produced by resistant bacteria. In Colombia, this problem has been studied mainly from the clinical perspective; however, it is scarcely studied in the leachates [...] Read more.
Antibiotic resistance is one of the main challenges worldwide due to the high morbidity and mortality caused by infections produced by resistant bacteria. In Colombia, this problem has been studied mainly from the clinical perspective; however, it is scarcely studied in the leachates produced in landfills. The objective of this study was to detect, identify and determine the antibiotic sensitivity profile of Enterobacterales isolated from a leachate treatment plant located in Cali, Colombia. Detection was performed using selective culture media, bacterial identification using Matrix-Assisted Laser Desorption/Ionization-Time-Of-Flight (MALDI-TOF, bioMérieux) and by sequencing the gene coding for the 16S ribosomal RNA subunit when discrepancies were observed between phenotypic characteristics and MALDI-TOF. Antibiotic sensitivity profiling was determined using the automated VITEK®2 system (bioMérieux). Twenty-one isolates were obtained, of which Klebsiella pneumoniae was the most frequent (23.8%), and 34% of the isolates showed decreased sensitivity to beta-lactam antibiotics such as cefoxitin, ampicillin/sulbactam and piperacillin/tazobactam. These findings suggest that leachates from landfills could be a reservoir of pathogenic bacteria carrying antibiotic resistance determinants, so periodic microbiological characterization of these effluents should be performed, promoting the One Health approach. Full article
(This article belongs to the Special Issue Dynamics and Molecular Features of Multidrug-Resistant Enterobacterales Lineages in Global Dissemination in a One Health Context (Humans, Animals, and Environment))
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14 pages, 1009 KiB  
Article
Lineages, Virulence Gene Associated and Integrons among Extended Spectrum β-Lactamase (ESBL) and CMY-2 Producing Enterobacteriaceae from Bovine Mastitis, in Tunisia
by Ahlem Jouini, Amira Klibi, Souhir Kmiha, Safa Hamrouni, Abdeljelil Ghram and Abderrazak Maaroufi
Pathogens 2022, 11(8), 948; https://doi.org/10.3390/pathogens11080948 - 22 Aug 2022
Cited by 6 | Viewed by 1988
Abstract
Extended Spectrum Beta-Lactamase (ESBL) Enterobacteriaceae are becoming widespread enzymes in food-producing animals worldwide. Escherichia coli and Klebseilla pneumoniae are two of the most significant pathogens causing mastitis. Our study focused on the characterization of the genetic support of ESBL/pAmpC and antibiotic resistance mechanisms [...] Read more.
Extended Spectrum Beta-Lactamase (ESBL) Enterobacteriaceae are becoming widespread enzymes in food-producing animals worldwide. Escherichia coli and Klebseilla pneumoniae are two of the most significant pathogens causing mastitis. Our study focused on the characterization of the genetic support of ESBL/pAmpC and antibiotic resistance mechanisms in cefotaxime-resistant (CTXR) and susceptible (CTXS) Enterobacteriaceae isolates, recovered from bovine mastitis in Tunisia, as well as the analyses of their clonal lineage and virulence-associated genes. The study was carried out on 17 ESBL/pAmpC E. coli and K. pneumoniae and 50 CTXS E. coli. Detection of resistance genes and clonal diversity was performed by PCR amplification and sequencing. The following β-lactamase genes were detected: blaCTX-M-15 (n = 6), blaCTX-M-15 + blaOXA-1 (2), bla CTX-M-15 + blaOXA-1 + blaTEM-1b (2), blaCTX-M-15 + blaTEM-1b (4), blaCMY-2 (3). The MLST showed the following STs: ST405 (n = 4 strains); ST58 (n = 3); ST155 (n = 3); ST471 (n = 2); and ST101 (n = 2). ST399 (n = 1) and ST617 (n = 1) were identified in p(AmpC) E. coli producer strains. The phylogroups A and B1 were the most detected ones, followed by the pathogenic phylogroup B2 that harbored the shigatoxin genes stx1/stx2, associated with the cnf, fimA, and aer virulence factors. The qnrA/qnrB, aac(6′)-Ib-cr genes and integrons class 1 with different gene cassettes were detected amongst these CTXR/S isolated strains. The presence of different genetic lineages, associated with resistance and virulence genes in pathogenic bacteria in dairy farms, may complicate antibiotic therapies and pose a potential risk to public health. Full article
(This article belongs to the Special Issue Dynamics and Molecular Features of Multidrug-Resistant Enterobacterales Lineages in Global Dissemination in a One Health Context (Humans, Animals, and Environment))
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15 pages, 1566 KiB  
Article
Prevalence and Molecular Characterization of Extended-Spectrum β-Lactamases and AmpC β-lactamase-Producing Enterobacteriaceae among Human, Cattle, and Poultry
by Mohamed A. Nossair, Fatma A. Abd El Baqy, Mohammad S. Y. Rizk, Haitham Elaadli, Alaa M. Mansour, Ayman H. Abd El-Aziz, Adil Alkhedaide, Mohamed Mohamed Soliman, Hazem Ramadan, Mustafa Shukry and Sabah I. Shaaban
Pathogens 2022, 11(8), 852; https://doi.org/10.3390/pathogens11080852 - 28 Jul 2022
Cited by 11 | Viewed by 2899
Abstract
Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are a universal public health alarm frequently identified among humans, animals, and poultry. Livestock and poultry production are a possible source of multidrug-resistant microorganisms, including ESBL-producing Enterobacteriaceae, which confer antimicrobial resistance to different β-lactam antimicrobial agents. From January [...] Read more.
Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are a universal public health alarm frequently identified among humans, animals, and poultry. Livestock and poultry production are a possible source of multidrug-resistant microorganisms, including ESBL-producing Enterobacteriaceae, which confer antimicrobial resistance to different β-lactam antimicrobial agents. From January to May 2020, a cross-sectional study was carried out in three dairy cattle farms and four poultry farms in different districts of northern Egypt to assess the prevalence of ESBLs, AmpC beta-lactamase-producing E. coli and Klebsiella in livestock, poultry, and human contacts, and to investigate the genetic relatedness of the recovered isolates. In total, 140 samples were collected, including human fecal samples (n = 20) of workers with intimate livestock contact, cattle rectal swabs (n = 34), milk (n = 14), milking machine swabs (n = 8), rations (n = 2), and water (n = 2) from different cattle farms, as well as cloacal swabs (n = 45), rations (n = 5), water (n = 5) and litter (n = 5) from poultry farms. The specimens were investigated for ESBL-producing E. coli and Klebsiella using HiCrome ESBL media agar. The agar disk diffusion method characterized the isolated strains for their phenotypic antimicrobial susceptibility. The prevalence of ESBL-producing Enterobacteriaceae was 30.0%, 20.0%, and 25.0% in humans, cattle, and poultry, respectively. Further genotypic characterization was performed using conventional and multiplex PCR assays for the molecular identification of ESBL and AmpC genes. The majority of the ESBL-producing Enterobacteriaceae showed a multi-drug resistant phenotype. Additionally, blaSHV was the predominant ESBL genotype (n = 31; 93.94%), and was mainly identified in humans (n = 6), cattle (n = 11), and poultry (14); its existence in various reservoirs is a concern, and highlights the necessity of the development of definite control strategies to limit the abuse of antimicrobial agents. Full article
(This article belongs to the Special Issue Dynamics and Molecular Features of Multidrug-Resistant Enterobacterales Lineages in Global Dissemination in a One Health Context (Humans, Animals, and Environment))
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18 pages, 1871 KiB  
Article
Genome Analysis of ESBL-Producing Escherichia coli Isolated from Pigs
by Luria Leslie Founou, Raspail Carrel Founou, Mushal Allam, Arshad Ismail and Sabiha Yusuf Essack
Pathogens 2022, 11(7), 776; https://doi.org/10.3390/pathogens11070776 - 7 Jul 2022
Cited by 12 | Viewed by 3111
Abstract
The resistome, virulome and mobilome of extended spectrum ß-lactamase (ESBL)-producing Escherichia coli (ESBL-Ec) isolated from pigs in Cameroon and South Africa were assessed using whole genome sequencing (WGS). Eleven clonally related phenotypic ESBL-Ec isolates were subjected to WGS. The prediction of antibiotic [...] Read more.
The resistome, virulome and mobilome of extended spectrum ß-lactamase (ESBL)-producing Escherichia coli (ESBL-Ec) isolated from pigs in Cameroon and South Africa were assessed using whole genome sequencing (WGS). Eleven clonally related phenotypic ESBL-Ec isolates were subjected to WGS. The prediction of antibiotic resistance genes, virulence factors (VFs) and plasmids was performed using ResFinder, VirulenceFinder and PlasmidFinder, respectively. Diverse sequence types (STs) were detected with ST2144 and ST88 being predominant and blaCTX-M-15 (55%) being the principal ESBL gene. All except two isolates harboured various aminoglycoside resistance genes, including aph(3″)-Ib (6/11, 55%) and aph(6)-1d (6/11, 55%), while the qnrS1 gene was identified in four of the isolates. The ESBL-Ec isolates showed a 93.6% score of being human pathogens. The fim, ehaB, ibeB/C were the leading virulence factors detected. All isolates harboured at least three extraintestinal pathogenic E. coli (ExPEC) VFs, with one isolate harbouring up to 18 ExPEC VFs. Five isolates (45.45%) harboured the plasmid incompatibility group IncF (FII, FIB, FIC, FIA). The study revealed that there is an urgent need to implement effective strategies to contain the dissemination of resistant and virulent ESBL-Ec through the food chain in Cameroon and South Africa. Full article
(This article belongs to the Special Issue Dynamics and Molecular Features of Multidrug-Resistant Enterobacterales Lineages in Global Dissemination in a One Health Context (Humans, Animals, and Environment))
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18 pages, 4519 KiB  
Article
Antimicrobial Resistance and Virulence Characteristics of Klebsiella pneumoniae Isolates in Kenya by Whole-Genome Sequencing
by Angela Muraya, Cecilia Kyany’a, Shahiid Kiyaga, Hunter J. Smith, Caleb Kibet, Melissa J. Martin, Josephine Kimani and Lillian Musila
Pathogens 2022, 11(5), 545; https://doi.org/10.3390/pathogens11050545 - 5 May 2022
Cited by 18 | Viewed by 5194
Abstract
Klebsiella pneumoniae is a globally significant opportunistic pathogen causing healthcare-associated and community-acquired infections. This study examined the epidemiology and the distribution of resistance and virulence genes in clinical K. pneumoniae strains in Kenya. A total of 89 K. pneumoniae isolates were collected over [...] Read more.
Klebsiella pneumoniae is a globally significant opportunistic pathogen causing healthcare-associated and community-acquired infections. This study examined the epidemiology and the distribution of resistance and virulence genes in clinical K. pneumoniae strains in Kenya. A total of 89 K. pneumoniae isolates were collected over six years from five counties in Kenya and were analyzed using whole-genome sequencing and bioinformatics. These isolates were obtained from community-acquired (62/89) and healthcare-associated infections (21/89), and from the hospital environment (6/89). Genetic analysis revealed the presence of blaNDM-1 and blaOXA-181 carbapenemase genes and the armA and rmtF genes known to confer pan-aminoglycoside resistance. The most abundant extended-spectrum beta-lactamase genes identified were blaCTX-M-15 (36/89), blaTEM (35/89), and blaOXA (18/89). In addition, one isolate had a mobile colistin resistance gene (mcr-8). Fluoroquinolone resistance-conferring mutations in gyrA and parC genes were also observed. The most notable virulence factors were those associated with hyper-virulence (rmpA/A2 and magA), yersiniabactin (ybt), salmochelin (iro), and aerobactin (iuc and iutA). A total of 38 distinct sequence types were identified, including known global lineages ST14, ST15, ST147, and ST307, and a regional clone ST17 implicated in regional outbreaks. In addition, this study genetically characterized two potential hypervirulent isolates and two community-acquired ST147 high-risk clones that contained carbapenemase genes, yersiniabactin, and other multidrug resistance genes. These results demonstrate that the resistome and virulome of Kenyan clinical and hospital environmental K. pneumoniae isolates are diverse. The reservoir of high-risk clones capable of spreading resistance, and virulence factors have the potential to cause unmanageable infection outbreaks with high morbidity and mortality. Full article
(This article belongs to the Special Issue Dynamics and Molecular Features of Multidrug-Resistant Enterobacterales Lineages in Global Dissemination in a One Health Context (Humans, Animals, and Environment))
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13 pages, 834 KiB  
Article
Multidrug-Resistant and Extended-Spectrum β-Lactamase (ESBL) - Producing Enterobacterales Isolated from Carriage Samples among HIV Infected Women in Yaoundé, Cameroon
by Ravalona Jessica Zemtsa, Michel Noubom, Luria Leslie Founou, Brice Davy Dimani, Patrice Landry Koudoum, Aurelia Djeumako Mbossi, Charles Kouanfack and Raspail Carrel Founou
Pathogens 2022, 11(5), 504; https://doi.org/10.3390/pathogens11050504 - 24 Apr 2022
Cited by 5 | Viewed by 3186
Abstract
The exacerbation of antimicrobial resistance (AMR) is a major public health threat worldwide. In sub-Saharan Africa, there is a scarcity of data regarding multidrug-resistant (resistance to at least one antibiotic of three or more families of antibiotics) as well as extended spectrum β-lactamase-producing [...] Read more.
The exacerbation of antimicrobial resistance (AMR) is a major public health threat worldwide. In sub-Saharan Africa, there is a scarcity of data regarding multidrug-resistant (resistance to at least one antibiotic of three or more families of antibiotics) as well as extended spectrum β-lactamase-producing Enterobacterales (ESBL-PE), isolated among clinical and asymptomatically healthy patients, especially in women living with HIV (WLHIV) despite their immunocompromised status. The overarching aim of this study was set to determine the prevalence and characterize genotypically multi-drug resistant Enterobacterales (MDR-E) and ESBL- PE isolated from vaginal swabs of WLHIV attending the Yaoundé Central Hospital, Yaoundé, Cameroon. A cross-sectional study was conducted among WLHIV during a four-month periods from 1 February to 31 May 2021. A total of 175 WLHIV, of childbearing age and under antiretroviral treatment were contacted. One hundred and twenty participants (120) were recruited and vaginal swabs were collected from them. After culture on Eosine-Methylen Blue (EMB) agar, the identification of Enterobacterales was performed using API 20E kit. A double-screening of ESBL-PE was performed using a combined disc diffusion method and ROSCO Diagnostica kits. An antibiotic susceptibility test was carried out by disc diffusion as per the Kirby-Bauer method and the β-lactamase resistance genes, blaCTX-M, blaCTX-M-group1-2-9, blaTEM were molecularly characterized using a conventional Polymerase Chain Reaction (PCR). Overall, 30.83% (37/120) of the included WLHIV were colonized with Enterobacterales and the prevalence of vaginal carriage of MDR Enterobacterales among them was 62.16% (23/37). Among MDR-E isolates, the most prevalent species were E. coli (56.0%; 14/25) and K. pneumoniae (20.0%; 5/25). High rates of resistance to trimethoprim-sulfamethoxazole (96.0%; 24/25), amoxicillin-clavulanic acid (88.0%; 22/25) and gentamicin (72%; 18/25) were observed. The resistance mechanisms detected among these isolates were ESBL (48.0%; 12/25), ESBL+ porin loss (8.0%; 2/25), ESBL+AmpC (24%; 6/25), with blaCTX-M, blaCTX-M-group-1,2,9 being identified at 48.0% (12/25) for each of them and blaTEM at 72.0% (18/25). Our findings confirm the high-prevalence of MDR as well as ESBL-PE isolated in WLHIV, and suggest that a real time monitoring system of antimicrobial resistant bacteria coupled with the reinforcement of infection prevention control (IPC) strategies are needed to sustainably contain these life-threatening pathogens especially in the most vulnerable populations. Full article
(This article belongs to the Special Issue Dynamics and Molecular Features of Multidrug-Resistant Enterobacterales Lineages in Global Dissemination in a One Health Context (Humans, Animals, and Environment))
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10 pages, 275 KiB  
Article
Increased Antibiotic Resistance in Children with Helicobacter pylori Infection: A Retrospective Study
by Luca Helmbold, Beniam Ghebremedhin, Aliyah Bellm, Marc A. Hopkins, Stefan Wirth and Malik Aydin
Pathogens 2022, 11(2), 178; https://doi.org/10.3390/pathogens11020178 - 27 Jan 2022
Cited by 10 | Viewed by 2642
Abstract
Children with recurrent abdominal pain may be suffering from a Helicobacterpylori (HP) infection. The gold standard for confirming HP gastritis is histological evaluation and microbiological tests performed on specimens collected by esophagogastroduodenoscopy (EGD). The aim of this study was to analyze HP [...] Read more.
Children with recurrent abdominal pain may be suffering from a Helicobacterpylori (HP) infection. The gold standard for confirming HP gastritis is histological evaluation and microbiological tests performed on specimens collected by esophagogastroduodenoscopy (EGD). The aim of this study was to analyze HP positive cultures and antibiograms with regard to clinical and histopathological correlates. The data of 124 subjects with frequent gastrointestinal symptoms who underwent an EGD were retrospectively collected and analyzed. The mean age of the patients was 13 ± 3.6 years. The most frequent complaints were epigastric pain (84%; n = 100/119) and dyspepsia (79%; n = 94/119). HP gastritis was diagnosed in 54% (n = 67). Interestingly, 40% (n = 49) of the isolates were resistant to at least one antibiotic: amoxicillin (20%; n = 10/49), clarithromycin (45%; n = 22/49), or metronidazole (59%; n = 29/49). Isolates were resistant to two or more antibiotics in 16% (n = 20) of cases. In conclusion, we revealed remarkably high resistance rates to amoxicillin, metronidazole, and clarithromycin in our cohort. The presence of antibiotic resistance to more than one antibiotic was substantially increased in our HP-infected patients and this may negatively affect eradication treatment. Full article
(This article belongs to the Special Issue Dynamics and Molecular Features of Multidrug-Resistant Enterobacterales Lineages in Global Dissemination in a One Health Context (Humans, Animals, and Environment))
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