bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Virulence Plasmid-Encoded
impCAB
Operon Enhances Survival and Induced Mutagenesis in
Shigella flexneri
after Exposure to UV Radiation
Authors: Runyen-Janecky Laura J. , Hong Mei , Payne Shelley M. 
Published: December 2019

ABSTRACT

Upon exposure to UV radiation,
Shigella flexneri
SA100 displayed survival and mutation frequencies comparable to those of
Escherichia coli
AB1157, which contains a functional UmuDC error-prone DNA repair system. Survival of SA100 after UV irradiation was associated with the presence of the 220-kb virulence plasmid, pVP. This plasmid encodes homologues of ImpA and ImpB, which comprise an error-prone DNA repair system encoded on plasmid TP110 that was initially identified in
Salmonella typhimurium
, and ImpC, encoded upstream of ImpA and ImpB. Although the
impB
gene was present in representatives of all four species of
Shigella
, not all isolates tested contained the gene.
Shigella
isolates that lacked
impB
were more sensitive to UV radiation than isolates that contained
impB
. The nucleotide sequence of a 2.4-kb DNA fragment containing the
imp
operon from
S. flexneri
SA100 pVP was 96% identical to the
imp
operon from the plasmid TP110. An SA100 derivative with a mutation in the
impB
gene had reduced survival following UV irradiation and less UV-induced mutagenesis relative to the parental strain. We also found that
S. flexneri
contained a chromosomally encoded
umuDC
operon; however, the
umuDC
promoter was not induced by exposure to UV radiation. This suggests that the
imp
operon but not the
umuDC
operon contributes to survival and induced mutagenesis in
S. flexneri
following exposure to UV radiation.
Lipopolysaccharide (LPS) from
Burkholderia cepacia
Is More Active than LPS from
Pseudomonas aeruginosa
and
Stenotrophomonas maltophilia
in Stimulating Tumor Necrosis Factor Alpha from Human Monocytes
Authors: Zughaier Susu M. , Ryley Henry C. , Jackson Simon K. 
Published: December 2019

ABSTRACT

Whole cells and lipopolysaccharides (LPSs) extracted from
Burkholderia cepacia
,
Pseudomonas aeruginosa
,
Stenotrophomonas maltophilia
, and
Escherichia coli
were compared in their ability to stimulate tumor necrosis factor alpha (TNF-α) from the human monocyte cell line MonoMac-6.
B. cepacia
LPS, on a weight-for-weight basis, was found to have TNF-α-inducing activity similar to that of LPS from
E. coli
, which was approximately four- and eightfold greater than the activity of LPSs from
P. aeruginosa
and
S. maltophilia
, respectively. The LPS-stimulated TNF-α production from monocytes was found to be CD14 dependent. These results suggest that
B. cepacia
LPS might play a role in the pathogenesis of inflammatory lung disease in cystic fibrosis, and in some patients it might be responsible, at least in part, for the sepsis-like cepacia syndrome.
Effects of Polysaccharide Fucoidin on Cerebrospinal Fluid Interleukin-1 and Tumor Necrosis Factor Alpha in Pneumococcal Meningitis in the Rabbit
Authors: Granert Carl , Raud Johan , Waage Anders , Lindquist Lars 
Published: December 2019

ABSTRACTThe inflammatory response in bacterial meningitis is mediated by cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1 (IL-1), which are produced in the subarachnoid space by different cells, e.g., leukocytes, astrocytes, and microglia. The recruitment of leukocytes into the cerebrospinal fluid (CSF) has been shown to contribute to the neurological damage in this disease, a process which could be enhanced by treatment with antibiotics. In this study, we have used a rabbit meningitis model for two sets of experiments with intracisternal (i.c.) injections ofStreptococcus pneumoniae. First, pneumococcal cell wall (PCW) components were injected i.c., inducing an inflammatory response with pleocytosis and increased levels of CSF TNF-α) and IL-1 at 6 and 12 h after PCW injection. Treatment with fucoidin, known to inhibit leukocyte rolling, abolished pleocytosis and inhibited the release of TNF-α and IL-1. In the second experiment, live pneumococcal bacteria were injected i.c. and treatment with one dose of ampicillin (40 mg/kg of body weight intravenously) was given 16 h after induction of meningitis, causing a sevenfold increase in CSF leukocytes over a 4-h period. CSF IL-1 levels at 16 h were high but did not increase further at 20 h. Also, CSF TNF-α levels were high at 16 h and tended to increase at 20 h. Fucoidin treatment prevented the antibiotic-induced increase of CSF leukocytes but had no effect on the TNF-α and IL-1 levels. Taken together, fucoidin reduced CSF TNF-α and IL-1 levels in acute bacterial meningitis induced by PCW fragments but had no effect later in the course of the disease, when live bacteria were used and an inflammatory increase was caused by a dose of antibiotics.
Immune Responses Induced in Cattle by Virulent and Attenuated
Mycobacterium bovis
Strains: Correlation of Delayed-Type Hypersensitivity with Ability of Strains To Grow in Macrophages
Authors: Wedlock D. Neil , Aldwell Frank E. , Collins Desmond M. , de Lisle Geoffrey W. , Wilson Theresa , Buddle Bryce M. 
Published: December 2019

ABSTRACT

Comparison of immune responses induced in cattle by virulent and attenuated strains of
Mycobacterium bovis
will assist in identifying responses associated with resistance or susceptibility to disease. Four strains of
M. bovis
, one which is virulent in guinea pigs (WAg201) and three which are attenuated in guinea pigs (an isoniazid-resistant strain [WAg405], ATCC 35721, and BCG) were compared for their abilities to induce immune responses in cattle and to grow in bovine lung alveolar macrophage cultures. Extensive macroscopic lesions were found only in cattle inoculated with the virulent
M. bovis
strain. Strong antibody responses to
M. bovis
culture filtrate, as well as persistently high levels of gamma interferon and interleukin-2 released from purified protein derivative (PPD)-stimulated peripheral blood lymphocyte cultures, were observed in the cattle inoculated with the virulent strain compared to those inoculated with the attenuated strains. All cattle inoculated with the virulent strain or two of the attenuated strains (WAg405 and ATCC 35721) elicited strong delayed-type hypersensitivity responses to PPD in skin tests, while animals inoculated with BCG induced only a weak response. The three strains which produced strong skin test responses proliferated well in bovine alveolar macrophages and induced high levels of proinflammatory cytokine mRNAs compared to BCG. Our study showed that skin test responsiveness to PPD correlated with the ability of the strains to grow in alveolar macrophages rather than to their pathogenicity in cattle.
Egg Laying Is Delayed but Worm Fecundity Is Normal in SCID Mice Infected withSchistosoma japonicumandS. mansoniwith or without Recombinant Tumor Necrosis Factor Alpha Treatment
Authors: Cheever Allen W. , Poindexter Robert W. , Wynn Thomas A. 
Published: December 2019

ABSTRACTMice with severe combined immunodeficiency (SCID mice) lack functional B and T cells. Egg laying bySchistosoma mansoniandS. japonicumwas delayed in SCID mice, but in a matter of weeks worm fecundity was equivalent to that in intact mice. SCID mice formed smaller hepatic granulomas and showed less fibrosis than did intact mice. The reduction in egg-associated pathology in SCID mice correlated with marked reductions in interleukin-4 (IL-4), IL-5, IL-13, and gamma interferon mRNA expression in the liver.S. mansoniinfections were frequently lethal for SCID mice infected for more than 9 weeks, whileS. japonicum-infected SCID mice died at the same rate as infected intact mice. We were unable to affect hepatic granuloma formation or egg laying by worms in SCID mice by administration of recombinant murine tumor necrosis factor alpha (TNF-α). In fact, SCID and BALB/c mice appeared to express nearly equivalent levels of TNF-α mRNA in their granulomatous tissues, suggesting that there is little or no deficit in TNF-α expression in infected SCID mice. The data indicate that TNF-α may be in large part derived from a non-T-cell source. Together, these findings provide little evidence that TNF-α alone can reconstitute early fecundity, granuloma formation, or hepatic fibrosis in schistosome-infected SCID mice.
Avidity as a Determinant of the Protective Efficacy of Human Antibodies to Pneumococcal Capsular Polysaccharides
Authors: Usinger William R. , Lucas Alexander H. 
Published: December 2019

ABSTRACTAntibodies reactive with capsular polysaccharides are considered the principal mediators of immunity against invasive diseases caused byStreptococcus pneumoniae. In this study, we tested the hypothesis that anti-pneumococcal capsular polysaccharide (PPS) antibody avidity can influence protective efficacy. We measured the avidities of individual adult postvaccination immunoglobulin G2 (IgG2) antibodies to PPS serotypes 6B and 23F and examined the relationship between avidity and opsonophagocytic and mouse-protective activities. The avidities of PPS 6B- and PPS 23F-specific IgG2 antibodies ranged from 6 to 31 nM−1and from 3 to 20 nM−1, respectively. We observed an inverse correlation between the magnitude of avidity and the amount of antibody required to protect mice against lethal bacteremia caused by serotype 6B pneumococci. Similarly, higher-avidity antibodies were more effective than lower-avidity antibodies in vitro in mediating complement-dependent opsonophagocytosis of both 6B and 23F pneumococci. These data suggest that in adults, PPS antibodies are sufficiently polymorphic to possess biologically significant variations in avidity. We conclude that avidity functions as an important determinant of anticapsular antibody protective efficacy against pneumococci.
Inverse Relationship between Severity of Experimental Pyelonephritis and Nitric Oxide Production in C3H/HeJ Mice
Authors: Nowicki Bogdan , Singhal Jyotsana , Fang Li , Nowicki Stella , Yallampalli Chandrasekhar 
Published: December 2019

ABSTRACTThe contribution of nitric oxide to host resistance to experimental pyelonephritis is not well understood. We examined whether the inhibition of nitric oxide synthesis alters the sensitivity of lipopolysaccharide (LPS) responder (C3H/HeN) and nonresponder (C3H/HeJ) mice to experimentalEscherichia colipyelonephritis. C3H/HeJ and C3H/HeN mice were implanted subcutaneously with minipumps containing an inhibitor of nitric oxide,NG-nitro-l-arginine methyl ester (l-NAME), or a corresponding vehicle. Ascending urinary tract infection by bladder catheterization with two strains ofE. coli, an O75 strain bearing Dr fimbriae and an O75 strain bearing P fimbriae, was developed in tested animals. Twenty-four hours following bladder infection, the kidneys of C3H/HeN and C3H/HeJ mice were colonized at a similar rate. However, 5 weeks postinoculation, C3H/HeN mice cleared infection while C3H/HeJ mice showed persistent colonization. Twenty-four hours following infection, C3H/HeN mice treated withl-NAME showed no significant increase of renal tissue infection compared to the saline-treated control group. However,l-NAME-treated C3H/HeJ mice showed an approximately 100-fold increase inE. coliinfection rate compared to the saline-treated controls in the Dr+group but showed no change compared to those in the P+group. Dissemination of Dr+E. colibut not P+E. colito the liver and uterus was significantly enhanced withl-NAME treatment in C3H/HeJ mice only. Nitric oxide had no direct killing effect onE. coliin vitro. Nitrite production by various organs was found to be significantly lower in C3H/HeJ mice than in C3H/HeN mice. Alteration of nitric oxide and LPS responsiveness was significantly associated with the increased sensitivity of C3H/HeJ mice to experimental Dr+but not to P+E. colipyelonephritis. These findings are consistent with the hypothesis that nitric oxide synthase activity in concert with LPS responsiveness may participate in the antibacterial defense mechanisms of the C3H mouse urinary tract. This phenomenon is strain dependent and possibly related to the invasive properties ofE. coli.
Phylogenetic Analysis of Enteroaggregative and Diffusely Adherent
Escherichia coli
Authors: Czeczulin John R. , Whittam Thomas S. , Henderson Ian R. , Navarro-Garcia Fernando , Nataro James P. 
Published: December 2019

ABSTRACT

The phylogenetics of the various pathotypes of diarrheagenic
Escherichia coli
are not completely understood. In this study, we identified several plasmid and chromosomal genes in the pathogenic enteroaggregative
E. coli
(EAEC) prototype strain 042 and determined the prevalence of these loci among EAEC and diffusely adherent
E. coli
strains. The distribution of these genes is analyzed within an evolutionary framework provided by the characterization of allelic variation in housekeeping genes via multilocus enzyme electrophoresis. Our data reveal that EAEC strains are heterogeneous with respect to chromosomal and plasmid-borne genes but that the majority harbor a member of a conserved family of virulence plasmids. Comparison of plasmid and chromosomal relatedness of strains suggests clonality of chromosomal markers and a limited transfer model of plasmid distribution.
Interruption of Multiple Cellular Processes in HT-29 Epithelial Cells by
Pseudomonas aeruginosa
Exoenzyme S
Authors: Olson Joan C. , Fraylick Jennifer E. , McGuffie Eileen M. , Dolan Katherine M. , Yahr Timothy L. , Frank Dara W. , Vincent Timothy S. 
Published: December 2019

ABSTRACT

Exoenzyme S (ExoS), an ADP-ribosylating enzyme produced by the opportunistic pathogen
Pseudomonas aeruginosa
, is directly translocated into eukaryotic cells by bacterial contact. Within the cell, ExoS ADP-ribosylates the cell signaling protein Ras and causes inhibition of DNA synthesis and alterations in cytoskeletal structure. To further understand the interrelationship of the different cellular effects of ExoS, functional analyses were performed on HT-29 epithelial cells after exposure to ExoS-producing
P. aeruginosa
388 and the non-ExoS-producing strain 388ΔS. Two different mechanisms of morphological alteration were identified: (i) a more-transient and less-severe cell rounding caused by the non-ExoS-producing strain 388ΔS and (ii) a more-severe, long-term cell rounding caused by ExoS-producing strain 388. Long-term effects of ExoS on cell morphology occurred in conjunction with ExoS-mediated inhibition of DNA synthesis and the ADP-ribosylation of Ras. ExoS was also found to cause alterations in HT-29 cell function, leading to the loss of cell adhesion and microvillus effacement. Nonadherent ExoS-treated cells remained viable but had a high proportion of modified Ras. While microvillus effacement was detected in both 388- and 388ΔS-treated cells, effacement was more prevalent and rapid in cells exposed to strain 388. We conclude from these studies that ExoS can have multiple effects on epithelial cell function, with more severe cellular alterations associated with the enzymatic modification of Ras. The finding that ExoS had greater effects on cell growth and adherence than on cell viability suggests that ExoS may contribute to the
P. aeruginosa
infectious process by rendering cells nonfunctional.
Structures inBacillus subtilisAre Recognized by CD14 in a Lipopolysaccharide Binding Protein-Dependent Reaction
Authors: Fan Xiaolong , Stelter Felix , Menzel Rene , Jack Robert , Spreitzer Ingo , Hartung Thomas , Schütt Christine 
Published: December 2019

ABSTRACTThe CD14 molecule expressed on monocytes and macrophages is a high-affinity receptor for bacterial lipopolysaccharide (LPS) and hence an important component of the innate immune system. LPS binding protein (LBP) is required to facilitate the binding of LPS to CD14 in vitro and is necessary for the induction of an inflammatory response to LPS in vivo. Here we show that CD14 and LBP can also bind to lipoteichoic acid from the gram-positive bacteriumBacillus subtilis. Although CD14 does not interact with intactB. subtilisorganisms, a brief exposure of the bacteria to serum converts them into a form which can bind to CD14 in an LBP-dependent reaction. When serum-pretreatedB. subtilisorganisms are incubated with the myelomonocytic cell line U937, which expresses CD14, the bacteria are rapidly phagocytosed. The phagocytosis is strictly dependent both on LBP and on CD14. These in vitro results suggest that LBP plays a role in the innate response not only to gram-negative but also to gram-positive infections.
A
Neisseria gonorrhoeae
Immunoglobulin A1 Protease Mutant Is Infectious in the Human Challenge Model of Urethral Infection
Authors: Johannsen Diana B. , Johnston David M. , Koymen Hakan O. , Cohen Myron S. , Cannon Janne G. 
Published: December 2019

ABSTRACT

Many mucosal pathogens, including
Neisseria gonorrhoeae
, produce proteases that cleave immunoglobulin A (IgA), the predominant immunoglobulin class produced at mucosal surfaces. While considerable circumstantial evidence suggests that IgA1 protease contributes to gonococcal virulence, there is no direct evidence that
N. gonorrhoeae
requires IgA1 protease activity to infect a human host. We constructed a
N. gonorrhoeae iga
mutant without introducing new antibiotic resistance markers into the final mutant strain and used human experimental infection to test the ability of the mutant to colonize the male urethra and to cause gonococcal urethritis. Four of the five male volunteers inoculated with the Iga
−
mutant became infected. In every respect—clinical signs and symptoms, incubation period between inoculation and infection, and the proportion of volunteers infected—the outcome of human experimental infection with FA1090
iga
was indistinguishable from that previously reported for a variant of parent strain FA1090 matching the mutant in expression of Opa proteins, lipooligosaccharide, and pilin. These results indicate that
N. gonorrhoeae
does not require IgA1 protease production to cause experimental urethritis in males.
Acute Clinical Disease in Cats following Infection with a Pathogenic Strain ofBartonella henselae(LSU16)
Authors: O’Reilly Kathy L. , Bauer Rudy W. , Freeland Rebecca L. , Foil Lane D. , Hughes Keith J. , Rohde Kristen R. , Roy Alma F. , Stout Rhett W. , Triche Patricia C. 
Published: December 2019

ABSTRACTBartonella henselaeis the causative agent of human cat scratch disease as well as several serious sequelae of infections, including bacillary angiomatosis and bacillary peliosis. Conflicting reports describe the pathogenesis ofB. henselaein the cat. In this study, we characterized a strain ofB. henselaetermed LSU16. This strain was isolated on rabbit blood agar from a naturally infected 10-month-old female cat during a recurrent episode of bacteremia. The bacterial species was confirmed by PCR-restriction fragment length polymorphism analysis. Nine cats were infected intradermally with 5 × 107CFU of LSU16, and clinical signs, antibody responses, and bacteremia were monitored. All nine cats developed raised, erythematous areas at the site of inoculation within 72 h postinoculation; the swelling peaked at 14 days postinfection and was not palpable by 28 days postinfection. Fever developed in all nine cats between 6 and 16 days postinfection and lasted for 1 to 8 days. Between 6 and 16 days postinfection, all nine cats experienced lethargy which persisted 5 to 18 days. Seven of nine cats were bacteremic by day 7, and all nine cats had become bacteremic by 14 days postinfection. Bacteremia peaked at 14 to 28 days postinfection in all cats. In six of the nine infected cats, bacterial numbers reached nondetectable levels during the 7th week postinfection; however, a single animal maintained bacteremia to 18 weeks postinfection. All nine cats developed strong antibody responses toB. henselae, as determined by Western blot analysis and enzyme-linked immunosorbent assay. Subsequently, three naive cats were injected intradermally with blood from cats infected with LSU16 from a pure culture, and five naive cats were injected with feces from fleas which had been feeding on cats infected with a pure culture of LSU16. These cats developed signs similar to those described in the previous experiment and were euthanized at 5 weeks postinfection. We conclude thatB. henselaeLSU16 is a virulent strain ofB. henselaein cats and propose that the virulence ofB. henselaein cats is strain dependent.
Proinflammatory Activation of Neutrophils and Monocytes byHelicobacter pyloriin Patients with Different Clinical Presentations
Authors: Hansen Per Syrak , Go Mae F. , Varming Kim , Andersen Leif P. , Genta Robert M. , Graham David Y. , Nielsen Henrik 
Published: December 2019

ABSTRACTChronicHelicobacter pyloriinfection is associated with mucosal inflammation. The aim of the present study was to assess human neutrophil and monocyte activation byH. pyloristrains obtained from patients with different clinical presentations. Bacterial sonicates from 12 strains were used to stimulate phagocyte upregulation of CD11b/CD18 adherence molecules assessed by fluorescence flow cytometry and oxidative burst responses assessed by chemiluminescence. A dose-dependent activation of CD11b/CD18 adherence molecules was observed with all strains on both neutrophils and monocytes. The activities were similar for strains from patients with duodenal ulceration and for strains from asymptomatic volunteers irrespective of histopathologic grades of the biopsy specimens from the antral mucosa. The neutrophil chemiluminescence response correlated with histopathologic severity. We conclude that upregulation of neutrophil and monocyte adherence molecules byH. pylorisonicates is not associated with clinical presentation of the infection.
Lymphotoxin InhibitsChlamydia pneumoniaeGrowth in HEp-2 Cells
Authors: Matsushima Hiroshi , Shirai Mutsunori , Ouchi Kazunobu , Yamashita Kenji , Kakutani Tetsu , Furukawa Susumu , Nakazawa Teruko 
Published: December 2019

ABSTRACTCytokines such as gamma interferon and tumor necrosis factor alpha (TNF-α) inhibit the intracellular replication ofChlamydia pneumoniaeorChlamydia trachomatis. In this study, we found that another cytokine, lymphotoxin (TNF-β), restricts the growth ofC. pneumoniaein HEp-2 cells. When lymphotoxin (10 U/ml) was added during incubation from 8 to 16 h postinoculation, inclusion body formation was severely reduced. In addition, we observed activation of nitric oxide production and the nuclear transition of NF-κB in HEp-2 cells in response to lymphotoxin. These results suggest that inhibition of chlamydial growth by lymphotoxin is mediated, at least in part, by nuclear transition of NF-κB, resulting in induction of nitric oxide synthase to produce nitric oxide, a potent bacteristatic agent. This is the first report on antichlamydial activity of lymphotoxin through induction of nitric oxide.
noxR3
, a Novel Gene from
Mycobacterium tuberculosis
, Protects
Salmonella typhimurium
from Nitrosative and Oxidative Stress
Authors: Ruan Jia , St. John Gregory , Ehrt Sabine , Riley Lee , Nathan Carl 
Published: December 2019

ABSTRACT

Reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) produced by activated macrophages participate in host defense against the facultative intracellular pathogens
Mycobacterium tuberculosis
and
Salmonella typhimurium
. To survive within macrophages, such pathogens may have evolved ROI and RNI resistance mechanisms. ROI resistance pathways have been intensively studied. Much less is known about the mechanisms of resistance to RNI. To identify possible RNI resistance genes in
M. tuberculosis
, a mycobacterial library was expressed in
S. typhimurium
and subjected to selection by exposure to the NO donor
S
-nitrosoglutathione (GSNO) in concentrations sufficient to kill the vast majority of nontransformed salmonellae. Among the rare surviving recombinants was a clone expressing
noxR3
, a novel and previously anonymous
M. tuberculosis
gene predicted to encode a small, basic protein. Expression of
noxR3
protected
S. typhimurium
not only from GSNO and acidified nitrite but also from H
2
O
2
.
noxR3
is the third gene cloned from
M. tuberculosis
that has been shown to protect heterologous cells from both RNI and ROI. This suggests diversity in the repertoire of mechanisms that help pathogens resist the oxidative and nitrosative defenses of the host.