#48: Perinatal Transmission of Multi-Drug Resistant Enterobacteriaceae

2021 ◽  
Vol 10 (Supplement_2) ◽  
pp. S14-S15
Author(s):  
Leena B Mithal ◽  
Aspen Kremer ◽  
Sebastian Otero ◽  
Sotirios N Markuly ◽  
Randy A McCool ◽  
...  
Keyword(s):  
Mouse Model ◽  
Perinatal Transmission ◽  
Coli Strain ◽  
International Travel ◽  
Transmission Model ◽  
Clinical Samples ◽  
Invasive Infection ◽  
Drug Resistant ◽  
E Coli ◽  
Gut Colonization

Abstract Background There is a global rise in multi-drug resistant (MDR) Gram-negative Enterobacteriaceae. Both maternal and neonatal gut colonization with pathogenic E. coli is associated with risk of invasive infection in infancy. Infections caused by MDR strains have delayed effective therapy and higher morbidity. Additionally, extended spectrum beta-lactamase producing (ESBL) E. coli are persistent gut colonizers. Perinatal transmission of ESBL E. coli could therefore have profound impact on the infant microbiota and health. Our aims were to 1) Determine the burden of ESBL Enterobacteriaceae (ESBL-E) colonization and rate of perinatal transmission among healthy mother-infant dyads in the Chicago area and 2) Compare rates of perinatal transmission among commensal, antibiotic-susceptible human E. coli strains versus ESBL E. coli strains in a mouse model. Methods This is an ongoing prospective study of healthy mothers and term infants born vaginally between 7/2020-11/2020. Maternal demographic and medical history data were collected, including age, race/ethnicity, international travel, and pregnancy/delivery information. Maternal rectal and vaginal swabs (n=62) were collected during labor. Clinical samples were initially grown in media supplemented with ampicillin and vancomycin to suppress growth of most susceptible commensal organisms. The sample was then plated on MacConkey agar (+/-ceftriaxone). We also developed a mouse model of perinatal transmission to determine the rate of transmission among ESBL E. coli compared to the commensal E. coli strain MG1655 and the pan-sensitive uropathogenic E. coli strain UTI89. Pups were sacrificed at 24–48 hours of life or 7 days of life, and presence of antibiotic resistant E. coli was noted. Results Human: Median maternal age was 32 years (IQR 30–35). Race was primarily white (84%), 11% Asian, and 10% were of Latina ethnicity. There were 30 (48%) female infants, and 42 (68%) infants received exclusive breastmilk. About half of the mothers reported international travel in the past 2 years (28/62, 45%), and 17/62 (27%) were born outside the USA. Ampicillin resistant (Amp-R) Enterobacteriaceae were recovered from rectal samples of 59/62 (95%) and vaginal samples of 16/62 (26%) mothers. Ten of 62 (16%) mothers were colonized with ESBL-E. Over half of infant stool samples (27/49, 55%) grew Amp-R Enterobacteriaceae. Of 6 mother-infant dyads with maternal ESBL-E colonization and infant stool available, 2 (33%) infants grew out ESBL-E. Murine We tested 4 ESBL E. coli strains and 2 control strains (MG1655 and UTI89) in our perinatal transmission model. We noted that while all strains adequately colonized the gut of the dams, only 2 (ST132 and ST511) of the 4 ESBL E. coli strains and none of the control strains were transmitted efficiently to the mouse pups (Figure 1). Conclusions There is notable community colonization of resistant Enterobacteriaceae among healthy mothers in Chicago with significant transmission to infants. Murine model data shows that human ESBL E. coli strains can colonize pregnant dams, and some ESBL E. coli strains appear to be perinatally transmitted more efficiently than non-drug resistant and commensal E. coli strains. Persistence of colonization, genomic factors related to transmission, and impact on the developing infant microbiome are future directions of study.

Characterization of the flexible genome complement of the commensal Escherichia coli strain A0 34/86 (O83 : K24 : H31)

Microbiology ◽  
2005 ◽  
Vol 151 (2) ◽  
pp. 385-398 ◽  
Author(s):  
Jana Hejnova ◽  
Ulrich Dobrindt ◽  
Radka Nemcova ◽  
Christophe Rusniok ◽  
Alojz Bomba ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Multiplex Pcr ◽  
Gene Clusters ◽  
Coli Strain ◽  
Bac Clone ◽  
Sequence Comparisons ◽  
Multiple Sequence ◽  
E Coli ◽  
Gut Colonization ◽  
K 12

Colonization by the commensal Escherichia coli strain A0 34/86 (O83 : K24 : H31) has proved to be safe and efficient in the prophylaxis and treatment of nosocomial infections and diarrhoea of preterm and newborn infants in Czech paediatric clinics over the past three decades. In searching for traits contributing to this beneficial effect related to the gut colonization capacity of the strain, the authors have analysed its genome by DNA–DNA hybridization to E. coli K-12 (MG1655) genomic DNA arrays and to ‘Pathoarrays’, as well as by multiplex PCR, bacterial artificial chromosome (BAC) library cloning and shotgun sequencing. Four hundred and ten E. coli K-12 ORFs were absent from A0 34/86, while 72 out of 456 genes associated with pathogenicity islands of E. coli and Shigella were also detected in E. coli A0 34/86. Furthermore, extraintestinal pathogenic E. coli-related genes involved in iron uptake and adhesion were detected by multiplex PCR, and genes encoding the HlyA and cytotoxic necrotizing factor toxins, together with 21 genes of the uropathogenic E. coli 536 pathogenicity island II, were identified by analysis of 2304 shotgun and 1344 BAC clone sequences of A0 34/86 DNA. Multiple sequence comparisons identified 31 kb of DNA specific for E. coli A0 34/86; some of the genes carried by this DNA may prove to be implicated in the colonization capacity of the strain, enabling it to outcompete pathogens. Among 100 examined BAC clones roughly covering the A0 34/86 genome, one reproducibly conferred on the laboratory strain DH10B an enhanced capacity to persist in the intestine of newborn piglets. Sequencing revealed that this BAC clone carried gene clusters encoding gluconate and mannonate metabolism, adhesion (fim), invasion (ibe) and restriction/modification functions. Hence, the genome of this clinically safe and highly efficient colonizer strain appears to harbour many ‘virulence-associated’ genes. These results highlight the thin line between bacterial ‘virulence’ and ‘fitness' or ‘colonization’ factors, and question the definition of enterobacterial virulence factors.

scholarly journals Synthesis and in Silico Modelling of the Potential Dual Mechanistic Activity of Small Cationic Peptides Potentiating the Antibiotic Novobiocin against Susceptible and Multi-Drug Resistant Escherichia coli

2020 ◽  
Vol 21 (23) ◽  
pp. 9134
Author(s):  
Ilaria Passarini ◽  
Pedro Ernesto de Resende ◽  
Sarah Soares ◽  
Tadeh Tahmasi ◽  
Paul Stapleton ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
In Silico ◽  
Mammalian Cells ◽  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Coli Strain ◽  
Cell Permeability ◽  
Cationic Peptides ◽  
Drug Resistant ◽  
E Coli

Cationic antimicrobial peptides have attracted interest, both as antimicrobial agents and for their ability to increase cell permeability to potentiate other antibiotics. However, toxicity to mammalian cells and complexity have hindered development for clinical use. We present the design and synthesis of very short cationic peptides (3–9 residues) with potential dual bacterial membrane permeation and efflux pump inhibition functionality. Peptides were designed based upon in silico similarity to known active peptides and efflux pump inhibitors. A number of these peptides potentiate the activity of the antibiotic novobiocin against susceptible Escherichia coli and restore antibiotic activity against a multi-drug resistant E. coli strain, despite having minimal or no intrinsic antimicrobial activity. Molecular modelling studies, via docking studies and short molecular dynamics simulations, indicate two potential mechanisms of potentiating activity; increasing antibiotic cell permeation via complexation with novobiocin to enable self-promoted uptake, and binding the E. coli RND efflux pump. These peptides demonstrate potential for restoring the activity of hydrophobic drugs.

scholarly journals Antibiotic resistance and detection of plasmid mediated colistin resistance mcr-1 gene among Escherichia coli and Klebsiella pneumoniae isolated from clinical samples

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Deepa Karki ◽  
Binod Dhungel ◽  
Srijana Bhandari ◽  
Anil Kunwar ◽  
Prabhu Raj Joshi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Drug Resistance ◽  
Klebsiella Pneumoniae ◽  
Clinical Samples ◽  
Gram Negative Bacteria ◽  
Beta Lactamase ◽  
Drug Resistant ◽  
Colistin Resistance ◽  
Gram Negative ◽  
E Coli

Abstract Background The prevalence of antimicrobial resistance (AMR) among Gram-negative bacteria is alarmingly high. Reintroduction of colistin as last resort treatment in the infections caused by drug-resistant Gram-negative bacteria has led to the emergence and spread of colistin resistance. This study was designed to determine the prevalence of drug-resistance among beta-lactamase-producing strains of Escherichia coli and Klebsiella pneumoniae, isolated from the clinical specimens received at a tertiary care centre of Kathmandu, Nepal during the period of March to August, 2019. Methods A total of 3216 different clinical samples were processed in the Microbiology laboratory of Kathmandu Model Hospital. Gram-negative isolates (E. coli and K. pneumoniae) were processed for antimicrobial susceptibility test (AST) by using modified Kirby-Bauer disc diffusion method. Drug-resistant isolates were further screened for extended-spectrum beta-lactamase (ESBL), metallo-beta-lactamase (MBL), carbapenemase and K. pneumoniae carbapenemase (KPC) production tests. All the suspected enzyme producers were processed for phenotypic confirmatory tests. Colistin resistance was determined by minimum inhibitory concentration (MIC) using agar dilution method. Colistin resistant strains were further screened for plasmid-mediated mcr-1 gene using conventional polymerase chain reaction (PCR). Results Among the total samples processed, 16.4% (529/3216) samples had bacterial growth. A total of 583 bacterial isolates were recovered from 529 clinical samples. Among the total isolates, 78.0% (455/583) isolates were Gram-negative bacteria. The most predominant isolate among Gram-negatives was E. coli (66.4%; 302/455) and K. pneumoniae isolates were 9% (41/455). In AST, colistin, polymyxin B and tigecycline were the most effective antibiotics. The overall prevalence of multidrug-resistance (MDR) among both of the isolates was 58.0% (199/343). In the ESBL testing, 41.1% (n = 141) isolates were confirmed as ESBL-producers. The prevalence of ESBL-producing E. coli was 43% (130/302) whereas that of K. pneumoniae was 26.8% (11/41). Similarly, 12.5% (43/343) of the total isolates, 10.9% (33/302) of E. coli and 24.3% of (10/41) K. pneumoniae were resistant to carbapenem. Among 43 carbapenem resistant isolates, 30.2% (13/43) and 60.5% (26/43) were KPC and MBL-producers respectively. KPC-producers isolates of E. coli and K. pneumoniae were 33.3% (11/33) and 20% (2/10) respectively. Similarly, 63.6% (21/33) of the E. coli and 50% (5/10) of the K. pneumoniae were MBL-producers. In MIC assay, 2.2% (4/179) of E. coli and 10% (2/20) of K. pneumoniae isolates were confirmed as colistin resistant (MIC ≥ 4 µg/ml). Overall, the prevalence of colistin resistance was 3.1% (6/199) and acquisition of mcr-1 was 16.6% (3/18) among the E. coli isolates. Conclusion High prevalence of drug-resistance in our study is indicative of a deteriorating situation of AMR. Moreover, significant prevalence of resistant enzymes in our study reinforces their roles in the emergence of drug resistance. Resistance to last resort drug (colistin) and the isolation of mcr-1 indicate further urgency in infection management. Therefore, extensive surveillance, formulation and implementation of effective policies, augmentation of diagnostic facilities and incorporation of antibiotic stewardship programs can be some remedies to cope with this global crisis.

scholarly journals Antimicrobial susceptibility of multi-drug and extensively-drug-resistant Escherichia coli to ceftolozane-tazobactam and ceftazidime-avibactam: An in vitro study*

2020 ◽  
Vol 74 ◽  
pp. 77-83
Author(s):  
Patrycja Zalas-Więcek ◽  
Eugenia Gospodarek-Komkowska
Keyword(s):  
Escherichia Coli ◽  
Therapeutic Options ◽  
Clinical Samples ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
E Coli ◽  
Extensively Drug Resistant

Aim: <i>Escherichia coli</i> is one of the Gram-negative bacteria, known to cause many nosocomial infections. Multi-drug (MDR) and extensively-drug resistant (XDR). <i>E. coli</i> are of particular note, due to significant limitations in antibiotic therapy. Ceftolozane-tazobactam and ceftazidime-avibactam are novel therapeutic options against Gram-negative bacteria; hence the aim of this study was to evaluate and compare the <i> in vitro </i> activity of ceftolozane-tazobactam and ceftazidime-avibactam against MDR and XDR clinical <i>E. coli</i> isolates. Material/Methods: The study included 100 non-replicate <i>E. coli</i> isolates derived from clinical samples of patients hospitalized in teaching hospitals. Bacteria were identified by applying mass spectrometry in the MALDI Biotyper system (Bruker). ESBL (bla<sub>CTX-M-1group</sub>, bla<sub>CTX-M-9group</sub>) and carbapenemase (bla<sub>KPC</sub>, bla<sub>VIM</sub>, bla<sub>NDM</sub>, bla<sub>OXA-48</sub>, bla<sub>OXA-181</sub>) genes were detected using the eazyplex® SuperBug CRE test, based on a loop-mediated isothermal amplification (LAMP). The in vitro susceptibility to ceftolozane-tazobactam and ceftazidime-avibactam was tested using validated MIC Test strips (Liofilchem). Results: All 84 extended-spectrum β-lactamase-producing (ESBL) <i>E. coli</i> isolates were susceptible to ceftazidime-avibactam and 83 to ceftolozane-tazobactam. Among 17 <i>E. coli</i> isolates with resistance to at least one of the carbapenems, three (17.6%) were susceptible to ceftolozane-tazobactam and ceftazidime-avibactam. All 14 blaVIM gene-positive <i>E. coli</i> isolates were resistant to both ceftolozane-tazobactam and ceftazidime-avibactam. Both antibiotics were active against bla<sub>CTX-M-9group</sub> and bla<sub>OXA-48</sub> gene-positive <i>E. coli</i> isolates, but they were not active against bla<sub>CTX-M-1group</sub> and bla<sub>VIM</sub> gene-positive isolates. Conclusions: Ceftolozane-tazobactam and ceftazidime-avibactam are alternative, non-carbapenem therapeutic options for ESBL-positive <i>E. coli</i> strains, and they are promising in the treatment of carbapenem-resistant <i>E. coli</i> strains, but not for those carrying the metallo-β-lactamase enzymes. Both drug combinations have comparable activity against ESBL, however, lower MIC values were found for ceftazidime-avibactam.

Detection of MCR-1 Gene in Multiple Drug Resistant Escherichia coli and Klebsiella pneumoniae in Human Clinical Samples from Peshawar, Pakistan

2020 ◽  
Vol 23 ◽  
Author(s):  
Fareeha Hameed ◽  
Muhammad Asif Khan ◽  
Hazrat Bilal ◽  
Hafsah Muhammad ◽  
Tayyab Ur Rehman
Keyword(s):  
Sequence Similarity ◽  
Tertiary Care ◽  
Health Concern ◽  
Diffusion Method ◽  
Clinical Samples ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Colistin Resistance ◽  
E Coli ◽  
Multiple Drug Resistant

Background: The presence of plasmid mediated mcr-1 gene in multidrug resistant Gram-negative bacteria poses a serious public health concern in today’s world. Objectives: The present study was aimed to detect the presence of plasmid mediated mcr-1 encoding resistance to colistin in multiple drug resistant (MDR) E. coli and K. pneumoniae isolates. Methods: A total 180 clinical isolates of E. coli (n=120) and K. pneumoniae (n=60) were isolated from different clinical specimens i.e. urine, blood, stool and pus, from diagnostic labs of two major public sector tertiary care hospitals in Peshawar, Pakistan. MDR profile of these isolates was assessed through Kirby-Baur disc diffusion method. All isolates were screened for colistin resistance by dilution methods. Colistin resistant isolates were subjected to PCR for mcr-1 detection and confirmation was done by Sanger sequencing method. Results: Overall 83.3% (100/120) E. coli and 93.3% (56/60) K. pneumoniae were detected as MDR. Colistin resistance was found in 23.3% (28/120) E. coli and 40% (24/60) K. pneumoniae isolates whereas mcr-1 gene was detected in 10 out of 52 colistin resistant isolates including six E. coli and four K. pneumoniae isolates. Minimum inhibitory concentrations (MICs) of colistin in these ten mcr-1 positive isolates ranged from 4µg/ml to 16µg/ml. All mcr-1 positive isolates showed 99% sequence similarity when compared with other present sequences in GenBank. Conclusion: Hence, our study confirms the presence of mcr-1 mediated colistin resistance in the studied area. Therefore, urgently larger scale surveillance studies are recommended to investigate prevalence of mcr-1 mediated colistin resistance and to prevent its further spread in the area.

scholarly journals Role of the Vpe Carbohydrate Permease in Escherichia coli Urovirulence and FitnessIn Vivo

2012 ◽  
Vol 80 (8) ◽  
pp. 2655-2666 ◽  
Author(s):  
Vanessa Martinez-Jéhanne ◽  
Christophe Pichon ◽  
Laurence du Merle ◽  
Olivier Poupel ◽  
Nadège Cayet ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Mouse Model ◽  
Sugar Transport ◽  
Gene Clusters ◽  
Content Type ◽  
E Coli ◽  
Healthy Humans ◽  
Gut Colonization

ABSTRACTUropathogenicEscherichia coli(UPEC) strains are a leading cause of infections in humans, but the mechanisms governing host colonization by this bacterium remain poorly understood. Previous studies have identified numerous gene clusters encoding proteins involved in sugar transport, in pathogen-specific islands. We investigated the role in fitness and virulence of thevpeoperon encoding an EII complex of the phosphotransferase (PTS) system, which is found more frequently in human strains from infected urine and blood (45%) than inE. coliisolated from healthy humans (15%). We studied the role of this locusin vivo, using the UPECE. colistrain AL511, mutants, and complemented derivatives in two experimental mouse models of infection. Mutant strains displayed attenuated virulence in a mouse model of sepsis. A role in kidney colonization was also demonstrated by coinfection experiments in a mouse model of pyelonephritis. Electron microscopy examinations showed that thevpeBCmutant produced much smaller amounts of a capsule-like surface material than the wild type, particularly when growing in human urine. Complementation of thevpeBCmutation led to an increase in the amount of exopolysaccharide, resistance to serum killing, and virulence. It was therefore clear that the loss ofvpegenes was responsible for all the observed phenotypes. We also demonstrated the involvement of thevpelocus in gut colonization in the streptomycin-treated mouse model of intestinal colonization. These findings confirm that carbohydrate transport and metabolism underlie the ability of UPEC strains to colonize the host intestine and to infect various host sites.

scholarly journals Isolation of bacteriophages from untreated sewage water against multi-drug resistant E.coli - An initiative to fight against drug resistance

2019 ◽  
Author(s):  
Hina Qamar ◽  
Mohd Owais ◽  
Dushyant Kumar Chauhan ◽  
Sumbul Rehman
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Therapeutic Potential ◽  
Alternative Therapy ◽  
Sewage Water ◽  
Coli Strain ◽  
Drug Resistant ◽  
Range Analysis ◽  
E Coli ◽  
Untreated Sewage

Abstract Background: Pathogenic Escherichia coli, common drinking water contaminant, cause a large number of morbidity and mortality worldwide. According to the WHO estimates approximately 63,000 annual deaths are due to E. coli infections. Due to selective pressure on coliforms, resistant microbial strains are produced that threatens modern medicine where common infections could become more deadly. So, there is an urgent need to develop alternative anti-microbial to replace existing antibiotics for treating a broad spectrum of bacterial diseases. This revived the interest of scientists in phages as an alternative therapy. Phage therapy is defined as a therapeutic use of bacteriophages (natural predators of bacteria) for treating bacterial infections. In the present study pure phage strain was isolated from the untreated sewage water sample and subjected to 10 fold dilution following double agar layer assay to determine phage titer against multi-drug resistant E.coli following host range analysis and stability testing at varying temperature and pH. Results: Sewage water contains a vast variety of different sizes bacteriophages with clear to diffused boundaries. The pure plaque isolated after repeated plating showed that it was highly specific against tested E. coli strain and could not lyse strains from other species. The titer was calculated to be 109 PFU/ml that remained unchanged at 4°C, 37°C and 50°C temperature. However, at higher pH range phage viability decreases. Conclusions: In future, it would be expected that the isolated bacteriophages could be characterized and used as a therapeutic potential against multi-drug resistant E.coli that not only attenuate superbug spread but could also replace antibiotics. Beside, isolated phages would be utilized as a bio-component in biosensor development against food borne pathogenic bacteria.

scholarly journals Impact of Bacteriophage-Supplemented Drinking Water on the E. coli Population in the Chicken Gut

Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 293 ◽  
Author(s):  
Sophie Kittler ◽  
Ruth Mengden ◽  
Imke H. E. Korf ◽  
Anna Bierbrodt ◽  
Johannes Wittmann ◽  
...  
Keyword(s):  
Drinking Water ◽  
No Reduction ◽  
Multidrug Resistant ◽  
Coli Strain ◽  
Resistant Bacteria ◽  
E Coli ◽  
Gut Colonization ◽  
Model Strain ◽  
Selection Of

Among intestinal coliform microbes in the broiler gut, there are potentially pathogenic Escherichia (E.) coli that can cause avian colibacillosis. The treatment with antibiotics favors the selection of multidrug-resistant bacteria and an alternative to this treatment is urgently required. A chicken model of intestinal colonization with an apathogenic model strain of E. coli was used to test if oral phage application can prevent or reduce the gut colonization of extraintestinal pathogenic E. coli variants in two individual experiments. The E. coli strain E28 was used as a model strain, which could be differentiated from other E. coli strains colonizing the broiler gut, and was susceptible to all cocktail phages applied. In the first trial, a mixture of six phages was continuously applied via drinking water. No reduction of the model E. coli strain E28 occurred, but phage replication could be demonstrated. In the second trial, the applied mixture was limited to the four phages, which showed highest efficacy in vitro. E. coli colonization was reduced in this trial, but again, no reduction of the E. coli strain E28 was observed. The results of the trials presented here can improve the understanding of the effect of phages on single strains in the multi-strain microbiota of the chicken gut.

scholarly journals Deciphering the Role of Colicins during Colonization of the Mammalian Gut by Commensal E. coli

2020 ◽  
Vol 8 (5) ◽  
pp. 664
Author(s):  
Amanda N. Samuels ◽  
Manuela Roggiani ◽  
Kathryn A. Smith ◽  
Jun Zhu ◽  
Mark Goulian ◽  
...  
Keyword(s):  
Natural Environment ◽  
Coli Strain ◽  
Microbial Populations ◽  
Potential Importance ◽  
Bacterial Survival ◽  
E Coli ◽  
Gut Colonization ◽  
Commensal Strain ◽  
Synthetic Models

Colicins are specific and potent toxins produced by Enterobacteriaceae that result in the rapid elimination of sensitive cells. Colicin production is commonly found throughout microbial populations, suggesting its potential importance for bacterial survival in complex microbial environments. Nonetheless, as colicin biology has been predominately studied using synthetic models, it remains unclear how colicin production contributes to survival and fitness of a colicin-producing commensal strain in a natural environment. To address this gap, we took advantage of MP1, an E. coli strain that harbors a colicinogenic plasmid and is a natural colonizer of the murine gut. Using this model, we validated that MP1 is competent for colicin production and then directly interrogated the importance of colicin production and immunity for MP1 survival in the murine gut. We showed that colicin production is dispensable for sustained colonization in the unperturbed gut. A strain lacking colicin production or immunity shows minimal fitness defects and can resist displacement by colicin producers. This report extends our understanding of the role that colicin production may play for E. coli during gut colonization and suggests that colicin production is not essential for a commensal to persist in its physiologic niche in the absence of exogenous challenges.

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