scholarly journals IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis

2010 ◽  
Vol 207 (6) ◽  
pp. 1307-1319 ◽  
Author(s):  
Rahul Mittal ◽  
Ignacio Gonzalez-Gomez ◽  
Ashok Panigrahy ◽  
Kerstin Goth ◽  
Richard Bonnet ◽  
...  

Ineffectiveness of antibiotics in treating neonatal Escherichia coli K1 meningitis and the emergence of antibiotic-resistant strains evidently warrants new prevention strategies. We observed that administration of interleukin (IL)-10 during high-grade bacteremia clears antibiotic-sensitive and -resistant E. coli from blood of infected mice. Micro-CT studies of brains from infected animals displayed gross morphological changes similar to those observed in infected human neonates. In mice, IL-10, but not antibiotic or anti-TNF antibody treatment prevented brain damage caused by E. coli. IL-10 administration elevated CR3 expression in neutrophils and macrophages of infected mice, whereas infected and untreated mice displayed increased expression of FcγRI and TLR2. Neutrophils or macrophages pretreated with IL-10 ex vivo exhibited a significantly greater microbicidal activity against E. coli compared with cells isolated from wild-type or IL-10−/− mice. The protective effect of IL-10 was abrogated when CR3 was knocked-down in vivo by siRNA. The increased expression of CR3 in phagocytes was caused by inhibition of prostaglandin E-2 (PGE-2) levels, which were significantly increased in neutrophils and macrophages upon E. coli infection. These findings describe a novel modality of IL-10–mediated E. coli clearance by diverting the entry of bacteria via CR3 and preventing PGE-2 formation in neonatal meningitis.

2007 ◽  
Vol 189 (14) ◽  
pp. 4975-4983 ◽  
Author(s):  
Blaine A. Legaree ◽  
Calvin B. Adams ◽  
Anthony J. Clarke

ABSTRACT Penicillin-binding protein 2 (PBP 2) has long been known to be essential for rod-shaped morphology in gram-negative bacteria, including Escherichia coli and Pseudomonas aeruginosa. In the course of earlier studies with P. aeruginosa PBP 2, we observed that E. coli was sensitive to the overexpression of its gene, pbpA. In this study, we examined E. coli overproducing both P. aeruginosa and E. coli PBP 2. Growth of cells entered a stationary phase soon after induction of gene expression, and cells began to lyse upon prolonged incubation. Concomitant with the growth retardation, cells were observed to have changed morphologically from typical rods into enlarged spheres. Inactive derivatives of the PBP 2s were engineered, involving site-specific replacement of their catalytic Ser residues with Ala in their transpeptidase module. Overproduction of these inactive PBPs resulted in identical effects. Likewise, overproduction of PBP 2 derivatives possessing only their N-terminal non-penicillin-binding module (i.e., lacking their C-terminal transpeptidase module) produced similar effects. However, E. coli overproducing engineered derivatives of PBP 2 lacking their noncleavable, N-terminal signal sequence and membrane anchor were found to grow and divide at the same rate as control cells. The morphological effects and lysis were also eliminated entirely when overproduction of PBP 2 and variants was conducted with E. coli MHD79, a strain lacking six lytic transglycosylases. A possible interaction between the N-terminal domain of PBP 2 and lytic transglycosylases in vivo through the formation of multienzyme complexes is discussed.


Author(s):  
Kingsley Ebomah ◽  
Martins Adefisoye ◽  
Anthony Okoh

The prevalence of pathogenic microorganisms, as well as the proliferation of antimicrobial resistance, pose a significant threat to public health. However, the magnitude of the impact of aquatic environs concerning the advent and propagation of resistance genes remains vague. Escherichia coli (E. coli) are widespread and encompass a variety of strains, ranging from non-pathogenic to highly pathogenic. This study reports on the incidence and antibiotic susceptibility profiles of E. coli isolates recovered from the Nahoon beach and its canal waters in South Africa. A total of 73 out of 107 (68.2%) Polymerase chain reaction confirmed E. coli isolates were found to be affirmative for at least one virulence factor. These comprised of enteropathogenic E. coli 11 (10.3%), enteroinvasive E. coli 14 (13.1%), and neonatal meningitis E. coli 48 (44.9%). The phenotypic antibiogram profiles of the confirmed isolates revealed that all 73 (100%) were resistant to ampicillin, whereas 67 (91.8%) of the pathotypes were resistant to amikacin, gentamicin, and ceftazidime. About 61 (83.6%) and 51 (69.9%) were resistant to tetracycline and ciprofloxacin, respectively, and about 21.9% (16) demonstrated multiple instances of antibiotic resistance, with 100% exhibiting resistance to eight antibiotics. The conclusion from our findings is that the Nahoon beach and its canal waters are reservoirs of potentially virulent and antibiotic-resistant E. coli strains, which thus constitute a potent public health risk.


Author(s):  
Jinghua Yang ◽  
Wei Ma ◽  
Yuanyuan Wu ◽  
Hui Zhou ◽  
Siyu Song ◽  
...  

Escherichia coli K1 is a leading cause of neonatal meningitis. The mortality and morbidity of this disease remain significantly high despite antibiotic therapy.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jin Zhang ◽  
Hongwu Sun ◽  
Chen Gao ◽  
Ying Wang ◽  
Xin Cheng ◽  
...  

Abstract Background Escherichia coli K1 (E. coli K1) caused neonatal meningitis remains a problem, which rises the urgent need for an effective vaccine. Previously, we rationally designed and produced the recombinant protein OmpAVac (Vo), which elicited protective immunity against E. coli K1 infection. However, Vo has limited stability, which hinders its future industrial application. Method Chitosan-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles were prepared and used as carried for the recombinant Vo. And the safety, stability and immunogenicity of Vo delivered by chitosan-modified PLGA nanoparticles were tested in vitro and in a mouse model of bacteremia. Results We successfully generated chitosan-modified PLGA nanoparticles for the delivery of recombinant Vo (VoNP). In addition, we found that a freeze-drying procedure increases the stability of the VoNPs without changing the shape, size distribution and encapsulation of the Vo protein. Unlike aluminum adjuvant, the nanoparticles that delivered Vo were immunoprotective in mice even after storage for as long as 180 days. Conclusions We identified an effective strategy to improve the stability of Vo to maintain its immunogenicity, which will contribute to the future development of vaccines against E. coli K1.


2005 ◽  
Vol 73 (5) ◽  
pp. 2923-2931 ◽  
Author(s):  
Ching-Hao Teng ◽  
Mian Cai ◽  
Sooan Shin ◽  
Yi Xie ◽  
Kee-Jun Kim ◽  
...  

ABSTRACT Escherichia coli K1 is a major gram-negative organism causing neonatal meningitis. E. coli K1 binding to and invasion of human brain microvascular endothelial cells (HBMEC) are a prerequisite for E. coli penetration into the central nervous system in vivo. In the present study, we showed using DNA microarray analysis that E. coli K1 associated with HBMEC expressed significantly higher levels of the fim genes compared to nonassociated bacteria. We also showed that E. coli K1 binding to and invasion of HBMEC were significantly decreased with its fimH deletion mutant and type 1 fimbria locked-off mutant, while they were significantly increased with its type 1 fimbria locked-on mutant. E. coli K1 strains associated with HBMEC were predominantly type 1 fimbria phase-on (i.e., fimbriated) bacteria. Taken together, we showed for the first time that type 1 fimbriae play an important role in E. coli K1 binding to and invasion of HBMEC and that type 1 fimbria phase-on E. coli is the major population interacting with HBMEC.


Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2005
Author(s):  
Céline Antoine ◽  
Fanny Laforêt ◽  
Bob Blasdel ◽  
Abdoulaye Fall ◽  
Jean-Noël Duprez ◽  
...  

Extra-intestinal Escherichia coli express several virulence factors that increase their ability to colonize and survive in different localizations. The K1 capsular type is involved in several infections, including meningitis, urinary tract, and bloodstream infections. The aims of this work were to isolate, characterize, and assess the in vivo efficacy of phages targeting avian pathogenic E. coli (APEC) O18:K1, which shares many similarities with the human strains responsible for neonatal meningitis. Eleven phages were isolated against APEC O18:K1, and four of them presenting a narrow spectrum targeting E. coli K1 strains were further studied. The newly isolated phages vB_EcoS_K1-ULINTec2 were similar to the Siphoviridae family, and vB_EcoP_K1-ULINTec4, vB_EcoP_K1-ULINTec6, and vB_EcoP_K1-ULINTec7 to the Autographiviridae family. They are capsular type (K1) dependent and present several advantages characteristic of lytic phages, such as a short adsorption time and latent period. vB_EcoP_K1-ULINTec7 is able to target both K1 and K5 strains. This study shows that these phages replicate efficiently, both in vitro and in vivo in the Galleria mellonella model. Phage treatment increases the larvae survival rates, even though none of the phages were able to eliminate the bacterial load.


2010 ◽  
Vol 76 (21) ◽  
pp. 7210-7216 ◽  
Author(s):  
Lucia Rivas ◽  
Brid Coffey ◽  
Olivia McAuliffe ◽  
Mary J. McDonnell ◽  
Catherine M. Burgess ◽  
...  

ABSTRACT This study investigated the effect of bacteriophages (phages) e11/2 and e4/1c against Escherichia coli O157:H7 in an ex vivo rumen model and in cattle in vivo. In the ex vivo rumen model, samples were inoculated with either 103 or 106 CFU/ml inoculum of E. coli O157:H7 and challenged separately with each bacteriophage. In the presence of phage e11/2, the numbers of E. coli O157:H7 bacteria were significantly (P < 0.05) reduced to below the limit of detection within 1 h. Phage e4/1c significantly (P < 0.05) reduced E. coli O157:H7 numbers within 2 h of incubation, but the number of surviving E. coli O157:H7 bacteria then remained unchanged over a further 22-h incubation period. The ability of a phage cocktail of e11/2 and e4/1c to reduce the fecal shedding of E. coli O157:H7 in experimentally inoculated cattle was then investigated in two cattle trials. Cattle (yearlings, n = 20 for trial one; adult fistulated cattle, n = 2 for trial two) were orally inoculated with 1010 CFU of E. coli O157:H7. Animals (n = 10 for trial one; n = 1 for trial two) were dosed daily with a bacteriophage cocktail of 1011 PFU for 3 days postinoculation. E. coli O157:H7 and phage numbers in fecal and/or rumen samples were determined over 7 days postinoculation. E. coli O157:H7 numbers rapidly declined in all animals within 24 to 48 h; however, there was no significant difference (P > 0.05) between the numbers of E. coli O157:H7 bacteria shed by the phage-treated or control animals. Phages were recovered from the rumen but not from the feces of the adult fistulated animal in trial two but were recovered from the feces of the yearling animals in trial one. While the results from the rumen model suggest that phages are effective in the rumen, further research is required to improve the antimicrobial effectiveness of phages for the elimination of E. coli O157:H7 in vivo.


2006 ◽  
Vol 74 (8) ◽  
pp. 4793-4800 ◽  
Author(s):  
Sheryl S. Justice ◽  
Scott R. Lauer ◽  
Scott J. Hultgren ◽  
David A. Hunstad

ABSTRACT Escherichia coli is the most common cause of community-acquired urinary tract infection (UTI). During murine cystitis, uropathogenic E. coli (UPEC) utilizes type 1 pili to bind and invade superficial bladder epithelial cells. UPEC then replicates within to form intracellular bacterial communities (IBCs), a process whose genetic determinants are as yet undefined. In this study, we investigated the role of SurA in the UPEC pathogenic cascade. SurA is a periplasmic prolyl isomerase/chaperone that facilitates outer membrane protein biogenesis and pilus assembly in E. coli. Invasion into bladder epithelial cells was disproportionately reduced when surA was genetically disrupted in the UPEC strain UTI89, demonstrating that binding alone is not sufficient for invasion. In a murine cystitis model, UTI89 surA::kan was unable to persist in the urinary tract. Complementation of UTI89 surA::kan with a plasmid (pDH15) containing surA under the control of an arabinose-inducible promoter restored in vivo binding and invasion events. However, the absence of arabinose within the mouse bladder resulted in depletion of SurA after invasion of the bacteria into the superficial epithelial cells. Under these conditions, invasion by UTI89/pDH15 surA::kan was normal, but in contrast to UTI89, UTI89/pDH15 surA::kan formed intracellular collections that contained fewer bacteria, were loosely organized, and lacked the normal transition to a densely packed, coccoid morphology. Our data argue that SurA is required within bladder epithelial cells for UPEC to undergo the morphological changes that underlie IBC maturation and completion of the UTI pathogenic cascade.


mBio ◽  
2012 ◽  
Vol 3 (6) ◽  
Author(s):  
Sarah L. Warnes ◽  
Callum J. Highmore ◽  
C. William Keevil

ABSTRACTHorizontal gene transfer (HGT) is largely responsible for increasing the incidence of antibiotic-resistant infections worldwide. While studies have focused on HGTin vivo, this work investigates whether the ability of pathogens to persist in the environment, particularly on touch surfaces, may also play an important role.Escherichia coli, virulent clone ST131, andKlebsiella pneumoniaeharboring extended-spectrum-β-lactamase (ESBL)blaCTX-M-15and metallo-β-lactamaseblaNDM-1, respectively, exhibited prolonged survival on stainless steel, with approximately 104viable cells remaining from an inoculum of 107 CFU per cm2after 1 month at 21°C. HGT ofblato an antibiotic-sensitive but azide-resistant recipientE. colistrain occurred on stainless steel dry touch surfaces and in suspension but not on dry copper. The conjugation frequency was approximately 10 to 50 times greater and occurred immediately, and resulting transconjugants were more stable with ESBLE. colias the donor cell than withK. pneumoniae, butblaNDM-1transfer increased with time. Transconjugants also exhibited the same resistance profile as the donor, suggesting multiple gene transfer. Rapid death, inhibition of respiration, and destruction of genomic and plasmid DNA of both pathogens occurred on copper alloys accompanied by a reduction inblacopy number. NakedE. coliDNA degraded on copper at 21°C and 37°C but slowly at 4°C, suggesting a direct role for the metal. Persistence of viable pathogenic bacteria on touch surfaces may not only increase the risk of infection transmission but may also contribute to the spread of antibiotic resistance by HGT. The use of copper alloys as antimicrobial touch surfaces may help reduce infection and HGT.IMPORTANCEHorizontal gene transfer (HGT) conferring resistance to many classes of antimicrobials has resulted in a worldwide epidemic of nosocomial and community infections caused by multidrug-resistant microorganisms, leading to suggestions that we are in effect returning to the preantibiotic era. While studies have focused on HGTin vivo, this work investigates whether the ability of pathogens to persist in the environment, particularly on touch surfaces, may also play an important role. Here we show prolonged (several-week) survival of multidrug-resistantEscherichia coliandKlebsiella pneumoniaeon stainless steel surfaces. Plasmid-mediated HGT of β-lactamase genes to an azide-resistant recipientE. colistrain occurred when the donor and recipient cells were mixed together on stainless steel and in suspension but not on copper surfaces. In addition, rapid death of both antibiotic-resistant strains and destruction of plasmid and genomic DNA were observed on copper and copper alloy surfaces, which could be useful in the prevention of infection spread and gene transfer.


2001 ◽  
Vol 90 (1) ◽  
pp. 261-268 ◽  
Author(s):  
Leonardo C. Clavijo ◽  
Mary B. Carter ◽  
Paul J. Matheson ◽  
Mark A. Wilson ◽  
William B. Wead ◽  
...  

In vivo pulmonary arterial catheterization was used to determine the mechanism by which platelet-activating factor (PAF) produces pulmonary edema in rats. PAF induces pulmonary edema by increasing pulmonary microvascular permeability (PMP) without changing the pulmonary pressure gradient. Rats were cannulated for measurement of pulmonary arterial pressure (Ppa) and mean arterial pressure. PMP was determined by using either in vivo fluorescent videomicroscopy or the ex vivo Evans blue dye technique. WEB 2086 was administered intravenously (IV) to antagonize specific PAF effects. Three experiments were performed: 1) IV PAF, 2) topical PAF, and 3) Escherichia coli bacteremia. IV PAF induced systemic hypotension with a decrease in Ppa. PMP increased after IV PAF in a dose-related manner. Topical PAF increased PMP but decreased Ppa only at high doses. Both PMP (88 ± 5%) and Ppa (50 ± 3%) increased during E. coli bacteremia. PAF-receptor blockade prevents changes in Ppa and PMP after both topical PAF and E. coli bacteremia. PAF, which has been shown to mediate pulmonary edema in prior studies, appears to act in the lung by primarily increasing microvascular permeability. The presence of PAF might be prerequisite for pulmonary vascular constriction during gram-negative bacteremia.


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