The ulcer-causing pathogen Helicobacter pylori uses directed motility, or chemotaxis, to both colonize the stomach and promote disease development. Previous work showed that mutants lacking the TlpB chemoreceptor, one of the receptors predicted to drive chemotaxis, led to less inflammation in the gerbil stomach than did the wild type. Here we expanded these findings and examined the effects on inflammation of completely nonchemotactic mutants and mutants lacking each chemoreceptor. Of note, all mutants colonized mice to the same levels as did wild-type H. pylori. Infection by completely nonchemotactic mutants (cheW or cheY) resulted in significantly less inflammation after both 3 and 6 months of infection. Mutants lacking either the TlpA or TlpB H. pylori chemotaxis receptors also had alterations in inflammation severity, while mutants lacking either of the other two chemoreceptors (TlpC and HylB) behaved like the wild type. Fully nonchemotactic and chemoreceptor mutants adhered to cultured gastric epithelial cells and caused cellular release of the chemokine interleukin-8 in vitro similar to the release caused by the wild type. The situation appeared to be different in the stomach. Using silver-stained histological sections, we found that nonchemotactic cheY or cheW mutants were less likely than the wild type to be intimately associated with the cells of the gastric mucosa, although there was not a strict correlation between intimate association and inflammation. Because others have shown that in vivo adherence promotes inflammation, we propose a model in which H. pylori uses chemotaxis to guide it to a productive interaction with the stomach epithelium.

ABSTRACTDifferent disease outcomes ofHelicobacter pyloriinfection correlate with distinct inflammation patterns. These different inflammatory distributions may be initiated by differences in bacterial localization. OneH. pyloriproperty known to affect murine stomach localization is chemotaxis, the ability to move in response to chemical cues. In this report, we used nonchemotactic mutants (Che−) to analyze whether chemotaxis is required for initial colonization of particular stomach regions or for subsequent growth therein. We found thatH. pyloribehaves differently in the corpus, antrum, and corpus-antrum transition zone subregions of the stomach. This outcome suggests that these regions contain unique chemotactic signals. In the corpus,H. pyloriutilizes chemotaxis for initial localization but not for subsequent growth. In contrast, in the antrum and the corpus-antrum transition zone, chemotaxis does not help initial colonization but does promote subsequent proliferation. To determine which chemoreceptor is responsible for the corpus-antrum phenotypes, we infected mice with strains lacking each chemoreceptor. Strains lacking TlpA, TlpB, or TlpC displayed only modest deviations from the wild-type phenotype, while strains lacking TlpD resembled the Che−mutant in their antral colonization defect and fared even worse than the Che−mutant in the corpus. Additional analysis showed that inflammation is worse in the antrum than in the corpus in both wild-type and Che−mutant infections. These results suggest that chemotaxis, specifically, that controlled by TlpD, is necessary forH. pylorito survive or grow in the environment of increased inflammation in the antrum.

bHelicobacter pylori infects over 3 billion people worldwide and is the primary risk factor for gastric cancer. Most individuals infected with H. pylori develop only asymptomatic gastritis; however, some develop ulcers or gastric adenocarcinoma. We demonstrate that one previously unappreciated parameter influencing H. pylori disease outcome is variation in the preinfection host microbiota. Utilizing a mouse model, we altered the microbiota by antibiotic treatment and found that these alterations resulted in significantly lowered H. pylori-triggered inflammation. Specifically, antibiotic pretreatment reduced CD4 ؉ T-helper cells and Ifn␥ transcript levels in gastric tissue after H. pylori infection. The bacterial communities in mice with a reduced response to H. pylori displayed many differences from those in untreated mice, including significantly more cluster IV and XIVa Clostridium spp., bacteria known to influence inflammation via regulatory T cell populations. Our findings suggest that microbiota composition, perhaps Clostridium spp., contributes to the variable disease outcome of H. pylori infection by altering the recruitment of CD4 ؉ T cells to the gastric compartment. Our results suggest that gastric microbiota could be used as a diagnostic tool to determine which patients are at risk for developing severe disease.

Empyema necessitatis is a rare complication of empyema in which the pleural infection spreads outside of the pleural space to involve the soft tissues of the chest wall. Most cases of empyema necessitatis are related to Mycobacterium tuberculosis and, less commonly, to Actinomyces spp. and Streptococcus spp. Staphylococcus aureus has rarely been reported as the causative agent of empyema necessitatis, with the majority of S. aureus isolates being methicillin sensitive. Only two cases of empyema necessitatis due to methicillin-resistant S. aureus (MRSA) have been reported in the medical literature. We report the case of a 59-year-old Caucasian male who presented to our institution with complaints of pain in and swelling of his left upper chest of 2-months duration. A computed tomography scan of the chest showed an 8.1-by 6.5-cm lesion which extended from the left upper lobe of the lung into the extrathoracic soft tissues beneath the left upper pectoralis muscle. A wedge resection of the left upper lung lobe revealed lung tissue with an organized pneumonia-like pattern associated with marked acute pleuritis. Blood and urine cultures and cultures of the left chest soft tissue mass grew MRSA. The patient was successfully treated with vancomycin followed by a 10-day outpatient course of ciprofloxacin and trimethoprim-sulfamethoxazole. This case represents an extremely rare manifestation of an increasingly dangerous bacterial pathogen. CASE REPORTA 59-year-old Caucasian male presented to our institution with complaints of progressive pain in and swelling of his left upper chest of 2-months duration. He had a significant past medical history of hypertension, insulin-dependent diabetes mellitus, chronic renal failure, cirrhosis, and bleeding esophageal varices requiring esophageal banding. He also had a history of heavy alcohol and tobacco use. On physical examination, his temperature was 98.1°F, his pulse was 71 beats per minute, his respiratory rate was 18 breaths per minute, his blood pressure was 142/84 mmHg, and his oxygen saturation was 97% on room air. His white blood cell count at the time of admission was 14.6. The patient's left upper chest wall was erythematous and tender to palpation. A computed tomography scan of the chest showed an 8.1-by 6.5-cm lesion which extended from the left upper lobe of the lung into the extrathoracic soft tissues beneath the left upper pectoralis muscle (Fig. 1). The central portion of the lesion showed fluid accumulation and air within the fluid-filled cavity. Erosion and bony destruction of the left lateral portion of the sternum and the distal end of the first rib were identified. Bilateral pleural effusions were present, and thrombosis of the left subclavian vein was seen. The radiographic differential diagnosis included abscess versus neoplasm. Blood cultures were drawn at the time of admission, and a subsequent Gram stain revealed Gram-positive cocci in clusters.The patient was started on empirical vancomycin therapy. Urine culture and susceptibility studies were performed t...

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