Role of Polymorphonuclear Neutrophils on Infectious Complications Stemming from Enterococcus faecalis Oral Infection in Thermally Injured Mice

Background: Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune system’s response to microbial pathogens through the release of reactive nitrogen species, including Nitric Oxide (NO). </P><P> Methods: In neutrophils, NO is produced by the inducible Nitric Oxide Synthase (iNOS), which is regulated by various signaling pathways and transcription factors. N-nitrosodimethylamine (NDMA), a potential human carcinogen, affects immune cells. NDMA plays a major part in the growing incidence of cancers. Thanks to the increasing knowledge on the toxicological role of NDMA, the environmental factors that condition the exposure to this compound, especially its precursors- nitrates arouse wide concern. Results: In this article, we present a detailed summary of the molecular mechanisms of NDMA’s effect on the iNOS-dependent NO production in human neutrophils. Conclusion: This research contributes to a more complete understanding of the mechanisms that explain the changes that occur during nonspecific cellular responses to NDMA toxicity.

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Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00236.2019 ◽

2020 ◽

Vol 318 (1) ◽

pp. G1-G9 ◽

Cited By ~ 2

Author(s):

Richard A. Jacobson ◽

Kiedo Wienholts ◽

Ashley J. Williamson ◽

Sara Gaines ◽

Sanjiv Hyoju ◽

...

Keyword(s):

Enterococcus Faecalis ◽

Healing Process ◽

Abdominal Sepsis ◽

Infectious Complications ◽

Fibrinolytic System ◽

Clinical Safety ◽

High Concentrations ◽

Clinically Significant

Perforations, anastomotic leak, and subsequent intra-abdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiological healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We (Shogan, BD et al. Sci Trans Med 7: 286ra68, 2015.) have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive degradation. Here, we demonstrate for the first time, to our knowledge, a novel collagenolytic virulence mechanism by which E. faecalis is able to bind and locally activate the human fibrinolytic protease plasminogen (PLG), a protein present in high concentrations in healing colonic tissue. E. faecalis-mediated PLG activation leads to supraphysiological collagen degradation; in this study, we demonstrate this concept both in vitro and in vivo. This pathoadaptive response can be mitigated with the PLG inhibitor tranexamic acid (TXA) in a fashion that prevents clinically significant complications in validated murine models of both E. faecalis- and Pseudomonas aeruginosa-mediated colonic perforation. TXA has a proven clinical safety record and is Food and Drug Administration approved for topical application in invasive procedures, albeit for the prevention of bleeding rather than infection. As such, the novel pharmacological effect described in this study may be translatable to clinical trials for the prevention of infectious complications in colonic healing. NEW & NOTEWORTHY This paper presents a novel mechanism for virulence in a commensal gut microbe that exploits the human fibrinolytic system and its principle protease, plasminogen. This mechanism is targetable by safe and effective nonantibiotic small molecules for the prevention of infectious complications in the healing gut.

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Role of mprF1 and mprF2 in the Pathogenicity of Enterococcus faecalis

PLoS ONE ◽

10.1371/journal.pone.0038458 ◽

2012 ◽

Vol 7 (6) ◽

pp. e38458 ◽

Cited By ~ 28

Author(s):

Yinyin Bao ◽

Tuerkan Sakinc ◽

Diana Laverde ◽

Dominique Wobser ◽

Abdellah Benachour ◽

...

Keyword(s):

Enterococcus Faecalis

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The Effect of Perioperative Administration of Probiotics on Colorectal Cancer Surgery Outcomes

Nutrients ◽

10.3390/nu13051451 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1451

Author(s):

Louise Pitsillides ◽

Gianluca Pellino ◽

Paris Tekkis ◽

Christos Kontovounisios

Keyword(s):

Colorectal Cancer ◽

Perioperative Management ◽

Single Species ◽

Infectious Complications ◽

Mucosal Permeability ◽

Colorectal Cancer Surgery ◽

Rate Analysis ◽

Surgery Outcomes ◽

Randomised Controlled

The perioperative care of colorectal cancer (CRC) patients includes antibiotics. Although antibiotics do provide a certain protection against infections, they do not eliminate them completely, and they do carry risks of microbial resistance and disruption of the microbiome. Probiotics can maintain the microbiome’s balance postoperatively by maintaining intestinal mucosal integrity and reducing bacterial translocation (BT). This review aims to assess the role of probiotics in the perioperative management of CRC patients. The outcomes were categorised into: postoperative infectious and non-infectious complications, BT rate analysis, and intestinal permeability assessment. Fifteen randomised controlled trials (RCTs) were included. There was a trend towards lower rates of postoperative infectious and non-infectious complications with probiotics versus placebo. Probiotics reduced BT, maintained intestinal mucosal permeability, and provided a better balance of beneficial to pathogenic microorganisms. Heterogeneity among RCTs was high. Factors that influence the effect of probiotics include the species used, using a combination vs. single species, the duration of administration, and the location of the bowel resection. Although this review provided evidence for how probiotics possibly operate and reported notable evidence that probiotics can lower rates of infections, heterogeneity was observed. In order to corroborate the findings, future RCTs should keep the aforementioned factors constant.

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Role for a Glycan Phosphoinositol Anchor in Fcγ Receptor Synergy

The Journal of Cell Biology ◽

10.1083/jcb.139.5.1209 ◽

1997 ◽

Vol 139 (5) ◽

pp. 1209-1217 ◽

Cited By ~ 35

Author(s):

Jennifer M. Green ◽

Alan D. Schreiber ◽

Eric J. Brown

Keyword(s):

T Cells ◽

Cell Types ◽

Polymorphonuclear Neutrophils ◽

Fcγ Receptor ◽

Fcγ Receptors ◽

Jurkat T Cells ◽

Gpi Anchor ◽

Transmembrane Anchor ◽

Activation Motif

While many cell types express receptors for the Fc domain of IgG (FcγR), only primate polymorphonuclear neutrophils (PMN) express an FcγR linked to the membrane via a glycan phosphoinositol (GPI) anchor. Previous studies have demonstrated that this GPI-linked FcγR (FcγRIIIB) cooperates with the transmembrane FcγR (FcγRIIA) to mediate many of the functional effects of immune complex binding. To determine the role of the GPI anchor in Fcγ receptor synergy, we have developed a model system in Jurkat T cells, which lack endogenously expressed Fcγ receptors. Jurkat T cells were stably transfected with cDNA encoding FcγRIIA and/or FcγRIIIB. Cocrosslinking the two receptors produced a synergistic rise in intracytoplasmic calcium ([Ca2+]i) to levels not reached by stimulation of either FcγRIIA or FcγRIIIB alone. Synergy was achieved by prolonged entry of extracellular Ca2+. Cocrosslinking FcγRIIA with CD59 or CD48, two other GPI-linked proteins on Jurkat T cells also led to a synergistic [Ca2+]i rise, as did crosslinking CD59 with FcγRIIA on PMN, suggesting that interactions between the extracellular domains of the two Fcγ receptors are not required for synergy. Replacement of the GPI anchor of FcγRIIIB with a transmembrane anchor abolished synergy. In addition, tyrosine to phenylalanine substitutions in the immunoreceptor tyrosine-based activation motif (ITAM) of the FcγRIIA cytoplasmic tail abolished synergy. While the ITAM of FcγRIIA was required for the increase in [Ca2+]i, tyrosine phosphorylation of crosslinked FcγRIIA was diminished when cocrosslinked with FcγRIIIB. These data demonstrate that FcγRIIA association with GPI-linked proteins facilitates FcγR signal transduction and suggest that this may be a physiologically significant role for the unusual GPI-anchored FcγR of human PMN.

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DETECTION OF HERPESVIRUS INFECTIONS IN CHILDREN OF THE FIRST SIX MONTHS OF LIFE

Journal of microbiology epidemiology immunobiology ◽

10.36233/0372-9311-2018-5-87-92 ◽

2018 ◽

pp. 87-92

Author(s):

E. M. Burmistrov ◽

T. N. Rybalkina ◽

N. V. Karazhas ◽

R. E. Boshyan ◽

P. A. Veselovsky ◽

...

Keyword(s):

Breast Milk ◽

Blood Cells ◽

Intrauterine Infection ◽

Infectious Complications ◽

Infectious Gastroenteritis ◽

Intestinal Infections ◽

Common Antigens ◽

Simplex Virus ◽

Positive Results

Aim. To evaluate a possible role of herpes viruses in the pathogenesis of various infectious diseases of children in the first six months of life, including acute gastroenteritis and identify the markers of herpesvirus infections which occur most frequently. Materials and methods. Samples of biological materials (blood serum and blood cells, breast milk, urine, feces) were studied in 35 children aged 14 days to 5 months who are being treated in MRRCI Vladimirsky with diagnoses of «acute infectious gastroenteritis of unspecified etiology» (n=24), «urinary tract infection» (n=6), «intrauterine infection» (n=5) and of their mothers. To determine the antibodies of IgM, IgG in serum, an enzyme immunoassay was used, to detect common antigens of viruses in blood cells, urine, breast milk - an indirect reaction of immunofluorescence, to detect early antigens of viruses and their reproduction - a rapid cultural method. Results. Infection with herpesviruses was found in 85% of children and 91% of mothers, with the most often identified markers of active forms of infection caused by the herpes simplex virus. In children with a diagnosis of acute infectious gastroenteritis of unspecified etiology, no pathogens of viral and bacterial intestinal infections were detected in a large number of active forms of herpesviral infections in both children and their mothers (33% and 91%, respectively). As well as mothers and their children, there have been cases of mixed infections caused by associations of herpesviruses, most often with HSV. Conclusion. Detection of active forms of herpesviral infections in the absence of positive results in studies on viral and bacterial intestinal infections make it possible to assume that herpesviruses can participate in the etiology of these diseases and cause infectious complications in this pathology, as well as often act as a co-infection. An important epidemiological importance has a large number of identified latent forms of herpesvirus infections, because when exposed to adverse factors they can go into active forms.

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Occurrence of urogenital mycoplasmas in men with the common genitourinary diseases

Brazilian Journal of Microbiology ◽

10.1007/s42770-021-00620-1 ◽

2021 ◽

Author(s):

Dominika Smolec ◽

Alicja Ekiel ◽

Piotr Kłuciński ◽

Jan Kawecki

Keyword(s):

Infectious Complications ◽

Prostatic Hyperplasia ◽

Control Group ◽

Study Group ◽

Immunocompromised Patients ◽

Healthy Men ◽

The Common ◽

Estimate Prevalence ◽

Positive Results

Abstract Many serious and fatal infections with urogenital mycoplasmas in immunocompromised patients have been reported. M. genitalium is recognized as a cause of male urethritis and other common genitourinary diseases. The aim of the study was to estimate prevalence of urogenital mycoplasmas which can cause complications in men with common genitourinary diseases. Study included 85 men with genitourinary tract carcinoma (n = 35), urolithiasis (n = 36), and BPH (benign prostatic hyperplasia) (n = 14). The control group consisted of 50 healthy men. FVU (first void urine) samples were examined by PCR for the presence of urogenital mycoplasmas DNA. Occurrence of urogenital mycoplasmas was significantly more common in study group compared with control 24/85 (28.2%) and 7/50 (14%), respectively (p = 0.05). In men with urolithiasis, positive results for mycoplasmas DNA were significantly more frequent than in control: 33.3% vs. 14% (p < 0.05). In patients with urolithiasis DNA of U. urealyticum was most often found, while in the genitourinary carcinoma and BPH groups, U. parvum was more frequent. Incidence of M. fermentans was also significantly higher in the urolithiasis group vs. control (p = 0.03). A higher percentage of positive results for urogenital mycoplasma DNA in study group has been found. Further studies are required to confirm the role of urogenital mycoplasmas in the development of infectious complications among patients with urolithiasis, genitourinary carcinoma, and BPH.

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The role of Enterococcus faecalis during co-infection with avian pathogenic Escherichia coli in avian colibacillosis

Avian Pathology ◽

10.1080/03079457.2020.1796926 ◽

2020 ◽

Vol 49 (6) ◽

pp. 589-599

Author(s):

Grayson K. Walker ◽

M. Mitsu Suyemoto ◽

Sesny Gall ◽

Laura Chen ◽

Siddhartha Thakur ◽

...

Keyword(s):

Escherichia Coli ◽

Enterococcus Faecalis ◽

Avian Pathogenic Escherichia Coli ◽

Pathogenic Escherichia Coli

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Intravascular chemoattractants inhibit diapedesis by selective receptor occupancy

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.260.2.h465 ◽

1991 ◽

Vol 260 (2) ◽

pp. H465-H472

Author(s):

G. Goldman ◽

R. Welbourn ◽

J. M. Klausner ◽

L. Kobzik ◽

C. R. Valeri ◽

...

Keyword(s):

Cell Migration ◽

Bronchoalveolar Lavage ◽

Receptor Occupancy ◽

Topical Administration ◽

Polymorphonuclear Neutrophils ◽

Oxidative Activity ◽

Cell Numbers ◽

Normal Plasma ◽

Lobar Bronchus

An extravascular chemoattractant leads to migration of polymorphonuclear neutrophils (PMN) to that site, whereas intravascular administration leads to PMN oxidative activity and sequestration in microvessels but no diapedesis. This study examines the inhibitory role of intravascular chemoattractants. Rabbits (n = 37) were pretreated with zymosan-activated plasma (ZAP), leukotriene (LT) B4, or thromboxane (Tx) mimic. These agents were given intra-arterially, topically into plastic chambers taped atop sites of dermabrasion on the back, or into a lobar bronchus (n = 35). Intra-arterial injection of each chemoattractant resulted, 10 min later, in a 29-42% increase in intracellular PMN H2O2. In saline-infused animals, topical administration of the chemoattractants into dermabrasion chambers resulted in PMN accumulation per cubic millimeter after 3 h of 600 with ZAP, 536 with LTB4, and 643 with Tx mimic; all values higher than 46 with saline and 63 with normal plasma (all P less than 0.05). In other saline-infused animals, lobar lung aspiration of chemoattractants led to diapedesis as measured in bronchoalveolar lavage (BAL) fluid (PMN x 10(4)/ml) after 3 h: 19.0 with ZAP, 11.2 with LTB4 and 14.5 with Tx mimic, all greater than aspiration with saline or normal plasma 4.0 and 4.9, respectively (all P less than 0.05). Intra-arterial chemotactic administration inhibited subsequent PMN diapedesis in response to that same chemoattractant, both in dermabrasion chambers and in BAL fluid. When different intra- and extra-vascular chemoattractants were used diapedesis was promoted. Thus Tx infused intra-arterially and ZAP applied to a blister or lobar bronchus led to rapid cell migration and increased cell numbers.(ABSTRACT TRUNCATED AT 250 WORDS)

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