scholarly journals Co-infection of H9N2 Influenza A Virus and Escherichia coli in a BALB/c Mouse Model Aggravates Lung Injury by Synergistic Effects

2021 ◽  
Vol 12 ◽  
Author(s):  
Song Wang ◽  
Ning Jiang ◽  
Wenhao Shi ◽  
Hang Yin ◽  
Xiaojuan Chi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Influenza Virus ◽  
Mouse Model ◽  
Influenza A ◽  
Bacterial Infections ◽  
Synergistic Effects ◽  
Scientific Basis ◽  
Bacteria Growth ◽  
E Coli ◽  
Nitric Oxide Synthase 2

Pathogens that cause respiratory diseases in poultry are highly diversified, and co-infections with multiple pathogens are prevalent. The H9N2 strain of avian influenza virus (AIV) and Escherichia coli (E. coli) are common poultry pathogens that limit the development of the poultry industry. This study aimed to clarify the interaction between these two pathogens and their pathogenic mechanism using a mouse model. Co-infection with H9N2 AIV and E. coli significantly increased the mortality rate of mice compared to single viral or bacterial infections. It also led to the development of more severe lung lesions compared to single viral or bacterial infections. Co-infection further causes a storm of cytokines, which aggravates the host’s disease by dysregulating the JAK/STAT/SOCS and ERK1/2 pathways. Moreover, co-infection mutually benefited the virus and the bacteria by increasing their pathogen loads. Importantly, nitric oxide synthase 2 (NOS2) expression was also significantly enhanced by the co-infection. It played a key role in the rapid proliferation of E. coli in the presence of the co-infecting H9N2 virus. Therefore, our study underscores the role of NOS2 as a determinant for bacteria growth and illustrates its importance as an additional mechanism that enhances influenza virus-bacteria synergy. It further provides a scientific basis for investigating the synergistic infection mechanism between viruses and bacteria.

scholarly journals Escherichia coli Genomic Diversity within Extraintestinal Acute Infections Argues for Adaptive Evolution at Play

mSphere ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Antoine Bridier-Nahmias ◽  
Adrien Launay ◽  
Alexandre Bleibtreu ◽  
Mélanie Magnan ◽  
Violaine Walewski ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Mouse Model ◽  
Bacterial Infections ◽  
Single Gene ◽  
Genomic Diversity ◽  
Mismatch Repair Gene ◽  
Content Type ◽  
E Coli ◽  
Synonymous Mutations ◽  
Acute Infections

ABSTRACT Adaptive processes in chronic bacterial infections are well described, but much less is known about the processes at play during acute infections. Here, by sequencing seven randomly selected isolates per patient, we analyzed Escherichia coli populations from three acute extraintestinal infections in adults (meningitis, pyelonephritis, and peritonitis), in which a high-mutation-rate isolate or mutator isolate was found. The isolates of single patients displayed between a few dozen and more than 200 independent mutations, with up to half being specific to the mutator isolate. Multiple signs of positive selection were evidenced: a high ratio of nonsynonymous to synonymous mutations (Ka/Ks ratio) and strong mutational convergence within and between patients, some of them at loci well known for their adaptive potential, such as rpoS, rbsR, fimH, and fliC. For all patients, the mutator isolate was likely due to a large deletion of a methyl-directed mismatch repair gene, and in two instances, the deletion extended to genes involved in some genetic convergence, suggesting potential coselection. Intrinsic extraintestinal virulence assessed in a mouse model of sepsis showed variable patterns of virulence ranging from non-mouse killer to mouse killer for the isolates from single patients. However, genomic signature and gene inactivation experiments did not establish a link between a single gene and the capacity to kill mice, highlighting the complex and multifactorial nature of the virulence. Altogether, these data indicate that E. coli isolates are adapting under strong selective pressure when colonizing an extraintestinal site. IMPORTANCE Little is known about the dynamics of adaptation in acute bacterial infections. By sequencing multiple isolates from monoclonal extraintestinal Escherichia coli infections in several patients, we were able to uncover traces of selection taking place at short time scales compared to chronic infection. High genomic diversity was observed in the patient isolates, with an excess of nonsynonymous mutations, and the comparison within and between different infections showed patterns of convergence at the gene level, both constituting strong signs of adaptation. The genes targeted were coding mostly for proteins involved in global regulation, metabolism, and adhesion/motility. Moreover, virulence assessed in a mouse model of sepsis was variable among the isolates of single patients, but this difference was left unexplained at the molecular level. This work gives us clues about the E. coli lifestyle transition between commensalism and pathogenicity.

scholarly journals Three-Year Trend in Escherichia coli Antimicrobial Resistance among Children’s Urine Cultures in an Italian Metropolitan Area

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 597
Author(s):  
Luca Pierantoni ◽  
Laura Andreozzi ◽  
Simone Ambretti ◽  
Arianna Dondi ◽  
Carlotta Biagi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Metropolitan Area ◽  
Bacterial Infections ◽  
Asymptomatic Bacteriuria ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
First Line ◽  
E Coli ◽  
First Line Therapy ◽  
Tract Infections

Urinary tract infections (UTIs) are among the most common bacterial infections in children, and Escherichia coli is the main pathogen responsible. Several guidelines, including the recently updated Italian guidelines, recommend amoxicillin-clavulanic acid (AMC) as a first-line antibiotic therapy in children with febrile UTIs. Given the current increasing rates of antibiotic resistance worldwide, this study aimed to investigate the three-year trend in the resistance rate of E. coli isolated from pediatric urine cultures (UCs) in a metropolitan area of northern Italy. We conducted a retrospective review of E. coli-positive, non-repetitive UCs collected in children aged from 1 month to 14 years, regardless of a diagnosis of UTI, catheter colonization, urine contamination, or asymptomatic bacteriuria. During the study period, the rate of resistance to AMC significantly increased from 17.6% to 40.2% (p < 0.001). Ciprofloxacin doubled its resistance rate from 9.1% to 16.3% (p = 0.007). The prevalence of multidrug-resistant E. coli rose from 3.9% to 9.2% (p = 0.015). The rate of resistance to other considered antibiotics remained stable, as did the prevalence of extended spectrum beta-lactamases and extensively resistant E. coli among isolates. These findings call into question the use of AMC as a first-line therapy for pediatric UTIs in our population, despite the indications of recent Italian guidelines.

scholarly journals Mechanistic insights into synergy between nalidixic acid and tetracycline against clinical isolates of Acinetobacter baumannii and Escherichia coli

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Amit Gaurav ◽  
Varsha Gupta ◽  
Sandeep K. Shrivastava ◽  
Ranjana Pathania
Keyword(s):  
Escherichia Coli ◽  
Acinetobacter Baumannii ◽  
Nalidixic Acid ◽  
Bacterial Infections ◽  
Clinical Isolates ◽  
Hospital Environment ◽  
Infection Model ◽  
Drug Resistant ◽  
E Coli

AbstractThe increasing prevalence of antimicrobial resistance has become a global health problem. Acinetobacter baumannii is an important nosocomial pathogen due to its capacity to persist in the hospital environment. It has a high mortality rate and few treatment options. Antibiotic combinations can help to fight multi-drug resistant (MDR) bacterial infections, but they are rarely used in the clinics and mostly unexplored. The interaction between bacteriostatic and bactericidal antibiotics are mostly reported as antagonism based on the results obtained in the susceptible model laboratory strain Escherichia coli. However, in the present study, we report a synergistic interaction between nalidixic acid and tetracycline against clinical multi-drug resistant A. baumannii and E. coli. Here we provide mechanistic insight into this dichotomy. The synergistic combination was studied by checkerboard assay and time-kill curve analysis. We also elucidate the mechanism behind this synergy using several techniques such as fluorescence spectroscopy, flow cytometry, fluorescence microscopy, morphometric analysis, and real-time polymerase chain reaction. Nalidixic acid and tetracycline combination displayed synergy against most of the MDR clinical isolates of A. baumannii and E. coli but not against susceptible isolates. Finally, we demonstrate that this combination is also effective in vivo in an A. baumannii/Caenorhabditis elegans infection model (p < 0.001)

Ability ofEscherichia coliO157:H7 isolates to colonize the intestinal tract of conventional adult CD1 mice is transient

2001 ◽  
Vol 47 (1) ◽  
pp. 91-95 ◽  
Author(s):  
J Wayne Conlan ◽  
Sonia L Bardy ◽  
Rhonda KuoLee ◽  
Ann Webb ◽  
Malcolm B Perry
Keyword(s):  
Escherichia Coli ◽  
Mouse Model ◽  
Intestinal Tract ◽  
Vaccine Development ◽  
Escherichia Coli O157 ◽  
Intestinal Colonization ◽  
E Coli ◽  
Cd1 Mice ◽  
A Current

In an attempt to improve upon a current mouse model of intestinal colonization by Escherichia coli O157:H7 used in this laboratory for vaccine development, nine clinical isolates of the pathogen were screened for their ability to persist in the intestinal tract of conventional adult CD-1 mice. None of the test isolates of E. coli O157:H7 were capable of colonizing these mice for a period of more than two weeks. Most of the isolates appeared to be benign for the experimental host, but one isolate was lethal. This virulence correlated with the ability of the latter isolate to produce large quantities of Shiga-like toxin 2 in vitro.

Alteration of the phagocytosis and antimicrobial defense of Octodonta nipae (Coleoptera: Chrysomelidae) pupae to Escherichia coli following parasitism by Tetrastichus brontispae (Hymenoptera: Eulophidae)

2018 ◽  
Vol 109 (2) ◽  
pp. 248-256
Author(s):  
E. Meng ◽  
J. Li ◽  
B. Tang ◽  
Y. Hu ◽  
T. Qiao ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune Response ◽  
Immune Responses ◽  
Mrna Expression ◽  
Bactericidal Activity ◽  
Bacterial Infections ◽  
Expression Level ◽  
Primary Immune Response ◽  
Mrna Expression Level ◽  
E Coli

AbstractAlthough parasites and microbial pathogens are both detrimental to insects, little information is currently available on the mechanism involved in how parasitized hosts balance their immune responses to defend against microbial infections. We addressed this in the present study by comparing the immune response between unparasitized and parasitized pupae of the chrysomelid beetle, Octodonta nipae (Maulik), to Escherichia coli invasion. In an in vivo survival assay, a markedly reduced number of E. coli colony-forming units per microliter was detected in parasitized pupae at 12 and 24 h post-parasitism, together with decreased phagocytosis and enhanced bactericidal activity at 12 h post-parasitism. The effects that parasitism had on the mRNA expression level of selected antimicrobial peptides (AMPs) of O. nipae pupae showed that nearly all transcripts of AMPs examined were highly upregulated during the early and late parasitism stages except defensin 2B, whose mRNA expression level was downregulated at 24 h post-parasitism. Further elucidation on the main maternal fluids responsible for alteration of the primary immune response against E. coli showed that ovarian fluid increased phagocytosis at 48 h post-injection. These results indicated that the enhanced degradation of E. coli in parasitized pupae resulted mainly from the elevated bactericidal activity without observing the increased transcripts of target AMPs. This study contributes to a better understanding of the mechanisms involved in the immune responses of a parasitized host to bacterial infections.

scholarly journals Multi-omic surveillance of Escherichia coli and Klebsiella spp. in hospital sink drains and patients

2020 ◽  
Author(s):  
B Constantinides ◽  
KK Chau ◽  
TP Quan ◽  
G Rodger ◽  
M Andersson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Resistance ◽  
Resistance Genes ◽  
Bacterial Infections ◽  
Wide Spectrum ◽  
Klebsiella Oxytoca ◽  
Clinical Disease ◽  
E Coli ◽  
Antimicrobial Resistance Genes ◽  
Wide Range

ABSTRACTEscherichia coli and Klebsiella spp. are important human pathogens that cause a wide spectrum of clinical disease. In healthcare settings, sinks and other wastewater sites have been shown to be reservoirs of antimicrobial-resistant E. coli and Klebsiella spp., particularly in the context of outbreaks of resistant strains amongst patients. Without focusing exclusively on resistance markers or a clinical outbreak, we demonstrate that many hospital sink drains are abundantly and persistently colonised with diverse populations of E. coli, Klebsiella pneumoniae and Klebsiella oxytoca, including both antimicrobial-resistant and susceptible strains. Using whole genome sequencing (WGS) of 439 isolates, we show that environmental bacterial populations are largely structured by ward and sink, with only a handful of lineages, such as E. coli ST635, being widely distributed, suggesting different prevailing ecologies which may vary as a result of different inputs and selection pressures. WGS of 46 contemporaneous patient isolates identified one (2%; 95% CI 0.05-11%) E. coli urine infection-associated isolate with high similarity to a prior sink isolate, suggesting that sinks may contribute to up to 10% of infections caused by these organisms in patients on the ward over the same timeframe. Using metagenomics from 20 sink-timepoints, we show that sinks also harbour many clinically relevant antimicrobial resistance genes including blaCTX-M, blaSHV and mcr, and may act as niches for the exchange and amplification of these genes. Our study reinforces the potential role of sinks in contributing to Enterobacterales infection and antimicrobial resistance in hospital patients, something that could be amenable to intervention.IMPORTANCEEscherichia coli and Klebsiella spp. cause a wide range of bacterial infections, including bloodstream, urine and lung infections. Previous studies have shown that sink drains in hospitals may be part of transmission chains in outbreaks of antimicrobial-resistant E. coli and Klebsiella spp., leading to colonisation and clinical disease in patients. We show that even in non-outbreak settings, contamination of sink drains by these bacteria is common across hospital wards, and that many antimicrobial resistance genes can be found and potentially exchanged in these sink drain sites. Our findings demonstrate that the colonisation of handwashing sink drains by these bacteria in hospitals is likely contributing to some infections in patients, and that additional work is needed to further quantify this risk, and to consider appropriate mitigating interventions.

scholarly journals A Host-Restricted Self-Attenuated Influenza Virus Provides Broad Pan-Influenza A Protection in a Mouse Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Minjin Kim ◽  
Yucheol Cheong ◽  
Jinhee Lee ◽  
Jongkwan Lim ◽  
Sanguine Byun ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Mouse Model ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Protective Efficacy ◽  
Influenza Viruses ◽  
Cross Protection ◽  
Infection Model ◽  
Wild Type ◽  
Group 1

Influenza virus infections can cause a broad range of symptoms, form mild respiratory problems to severe and fatal complications. While influenza virus poses a global health threat, the frequent antigenic change often significantly compromises the protective efficacy of seasonal vaccines, further increasing the vulnerability to viral infection. Therefore, it is in great need to employ strategies for the development of universal influenza vaccines (UIVs) which can elicit broad protection against diverse influenza viruses. Using a mouse infection model, we examined the breadth of protection of the caspase-triggered live attenuated influenza vaccine (ctLAIV), which was self-attenuated by the host caspase-dependent cleavage of internal viral proteins. A single vaccination in mice induced a broad reactive antibody response against four different influenza viruses, H1 and rH5 (HA group 1) and H3 and rH7 subtypes (HA group 2). Notably, despite the lack of detectable neutralizing antibodies, the vaccination provided heterosubtypic protection against the lethal challenge with the viruses. Sterile protection was confirmed by the complete absence of viral titers in the lungs and nasal turbinates after the challenge. Antibody-dependent cellular cytotoxicity (ADCC) activities of non-neutralizing antibodies contributed to cross-protection. The cross-protection remained robust even after in vivo depletion of T cells or NK cells, reflecting the strength and breadth of the antibody-dependent effector function. The robust mucosal secretion of sIgA reflects an additional level of cross-protection. Our data show that the host-restricted designer vaccine serves an option for developing a UIV, providing pan-influenza A protection against both group 1 and 2 influenza viruses. The present results of potency and breadth of protection from wild type and reassortant viruses addressed in the mouse model by single immunization merits further confirmation and validation, preferably in clinically relevant ferret models with wild type challenges.

scholarly journals Exogenous Activation of Invariant Natural Killer T Cells by α-Galactosylceramide Reduces Pneumococcal Outgrowth and Dissemination Postinfluenza

mBio ◽  
2016 ◽  
Vol 7 (6) ◽  
Author(s):  
Adeline Barthelemy ◽  
Stoyan Ivanov ◽  
Maya Hassane ◽  
Josette Fontaine ◽  
Béatrice Heurtault ◽  
...  
Keyword(s):  
Mouse Model ◽  
Influenza A Virus ◽  
Bacterial Pneumonia ◽  
Influenza A ◽  
Bacterial Infections ◽  
Pneumococcal Infection ◽  
Clinical Development ◽  
Inkt Cell ◽  
Inkt Cells ◽  
Invariant Natural Killer

ABSTRACT Influenza A virus infection can predispose to potentially devastating secondary bacterial infections. Invariant natural killer T (iNKT) cells are unconventional, lipid-reactive T lymphocytes that exert potent immunostimulatory functions. Using a mouse model of postinfluenza invasive secondary pneumococcal infection, we sought to establish whether α-galactosylceramide (α-GalCer [a potent iNKT cell agonist that is currently in clinical development]) could limit bacterial superinfection. Our results highlighted the presence of a critical time window during which α-GalCer treatment can trigger iNKT cell activation and influence resistance to postinfluenza secondary pneumococcal infection. Intranasal treatment with α-GalCer during the acute phase (on day 7) of influenza virus H3N2 and H1N1 infection failed to activate (gamma interferon [IFN-γ] and interleukin-17A [IL-17A]) iNKT cells; this effect was associated with a strongly reduced number of conventional CD103 + dendritic cells in the respiratory tract. In contrast, α-GalCer treatment during the early phase (on day 4) or during the resolution phase (day 14) of influenza was associated with lower pneumococcal outgrowth and dissemination. Less intense viral-bacterial pneumonia and a lower morbidity rate were observed in superinfected mice treated with both α-GalCer (day 14) and the corticosteroid dexamethasone. Our results open the way to alternative (nonantiviral/nonantibiotic) iNKT-cell-based approaches for limiting postinfluenza secondary bacterial infections. IMPORTANCE Despite the application of vaccination programs and antiviral drugs, influenza A virus (IAV) infection is responsible for widespread morbidity and mortality (500,000 deaths/year). Influenza infections can also result in sporadic pandemics that can be devastating: the 1918 pandemic led to the death of 50 million people. Severe bacterial infections are commonly associated with influenza and are significant contributors to the excess morbidity and mortality of influenza. Today’s treatments of secondary bacterial (pneumococcal) infections are still not effective enough, and antibiotic resistance is a major issue. Hence, there is an urgent need for novel therapies. In the present study, we set out to evaluate the efficacy of α-galactosylceramide (α-GalCer)—a potent agonist of invariant NKT cells that is currently in clinical development—in a mouse model of postinfluenza, highly invasive pneumococcal pneumonia. Our data indicate that treatment with α-GalCer reduces susceptibility to superinfections and, when combined with the corticosteroid dexamethasone, reduces viral-bacterial pneumonia.

scholarly journals Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages

2012 ◽  
Vol 57 (1) ◽  
pp. 189-195 ◽  
Author(s):  
Migla Miskinyte ◽  
Isabel Gordo
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Resistance Mutation ◽  
Fitness Cost ◽  
Resistance Mutations ◽  
Content Type ◽  
E Coli ◽  
Fitness Effects ◽  
K 12

ABSTRACTMutations causing antibiotic resistance usually incur a fitness cost in the absence of antibiotics. The magnitude of such costs is known to vary with the environment. Little is known about the fitness effects of antibiotic resistance mutations when bacteria confront the host's immune system. Here, we study the fitness effects of mutations in therpoB,rpsL, andgyrAgenes, which confer resistance to rifampin, streptomycin, and nalidixic acid, respectively. These antibiotics are frequently used in the treatment of bacterial infections. We measured two important fitness traits—growth rate and survival ability—of 12Escherichia coliK-12 strains, each carrying a single resistance mutation, in the presence of macrophages. Strikingly, we found that 67% of the mutants survived better than the susceptible bacteria in the intracellular niche of the phagocytic cells. In particular, allE. colistreptomycin-resistant mutants exhibited an intracellular advantage. On the other hand, 42% of the mutants incurred a high fitness cost when the bacteria were allowed to divide outside of macrophages. This study shows that single nonsynonymous changes affecting fundamental processes in the cell can contribute to prolonged survival ofE. coliin the context of an infection.

In vitro activity of antimicrobial agents with and without sulbactam, EDTA and sulbactam-EDTA on ESBLs-producing Escherichia coli isolated from healthy Tibetan yaks

2020 ◽  
Author(s):  
Baoguang Liu ◽  
Xiaoling Yuan ◽  
Yiheng Chen ◽  
Xiaoshen Li ◽  
Ming Bai ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Nasal Swab ◽  
Antimicrobial Agents ◽  
Synergistic Effects ◽  
E Coli ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Third Generation Cephalosporins ◽  
Enhance Activity

Abstract Background The spread of ESBLs-producing bacteria has been strikingly rapid in many regions of the world and it causes therapeutic difficulties in everyday practice. The aims of this study were to investigate the prevalence and susceptibilities of ESBLs-producing Escherichia coli isolates from healthy Tibetan yaks in China, to evaluate the activity of drug combinations on ESBLs-producing E. coli isolates. Methods From July 2018 to August 2019, a total of 750 nasal swab samples were tested for the presence of E. coli and ESBLs-producing strains. The MICs of 11 antimicrobial agents alone and combinations with sulbactam, EDTA or sulbactam-EDTA against 240 ESBLs-producing E.coli strains were determined by the broth microdilution method. Results Overall, 59.87% (n = 449) of the samples were positive for E. coli, 240 (53.45%) of 449 E. coli isolates were confirmed to be ESBLs-producing. The addition of sulbactam to the third generation cephalosporins, amikacin and fosfomycin for all isolates resulted in low MICs, increasing the level of susceptibility from 0, 0 and 0% to 50 ~ 87.5, 4.2 and 100% respectively. The addition of EDTA to fluoroquinolones, doxycycline, florfenicol, amikacin and fosfomycin, showed improved activities and resulted in low MICs, increasing the level of susceptibility from 0, 0, 8.3, 0 and 0% to 4.2 ~ 29.2, 33.3, 33.3, 66.7 and 45.8%, respectively. All other antibacterials (except fluoroquinolones, doxycycline and florfenicol), when combined with sulbactam-EDTA, were found to be more active than combinations only with sulbactam or with EDTA against most of isolates, with lower MIC50s and MIC90s. Conclusion In conclusion, ESBLs-producing E. coli isolates were widespread in healthy Tibetan yaks in China. ESBLs-producing E. coli isolates exhibited varying degrees of multidrug resistance. This study these findings suggested that sulbactam can enhance activity of β-lactams and some non-β-lactams of antimicrobial agents and had a synergistic effects with EDTA in improving activities of some families of antimicrobials.

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