Knockout mutations were constructed in the arcA gene of a virulent type b strain of Haemophilus influenzae, and the behavior of the resulting mutants was investigated in a number of conditions that mimicked distinct steps in the natural infection pathway. In arcA mutants, synthesis of capsule and lipooligosaccharide (LOS) and growth in synthetic media were unaltered compared to synthesis of capsule and LOS and growth in synthetic media in the wild-type H. influenzae type b parent strain. However, the virulence of the arcA mutants for BALB/c mice was significantly reduced. Upon exposure to human blood or serum, the arcA mutants showed markedly reduced survival compared with the survival of its wild-type parent. Serum resistance could be fully restored by complementation in cis with the H. influenzae arcA gene but not by complementation in cis with the homologous gene from Escherichia coli. The proteomes of wild-type and mutant bacteria were markedly different, especially under anaerobic conditions, underscoring the global regulatory role of ArcAB in H. influenzae. Evaluation of antibody titers and classical complement activities in various serum samples pointed to complement-mediated bactericidal activity as the factor that distinguishes between the arcA mutant and wild-type phenotypes. Comparative analysis of the membrane fractions of the arcA mutants and the wild-type strain revealed several ArcA-regulated proteins, some of which may be implicated in the serum hypersensitivity phenotype.The only known natural host of Haemophilus influenzae is humans. Carriage of unencapsulated H. influenzae in the nasopharyngeal area is common, especially among children, and is considered a probable source of infection in otitis media, sinusitis, and pneumonia (51). Life-threatening H. influenzae meningitis is caused mainly by encapsulated type b strains; this is attributed to several factors, including the resistance of these strains to bactericidal activities of blood. Passage from the upper respiratory mucosa via the general circulation to the meninges requires successive adaptations of a bacterium's physiology in order to cope with the environmental changes that it encounters. Although the roles of the type b capsule (61) and lipooligosaccharide (LOS) (57) in invasive disease have been clearly demonstrated, we know little about the roles of other virulence factors in H. influenzae infections, not in the least because of the lack of reliable animal models.We hypothesized that the capacity of H. influenzae to swiftly adapt its physiology to match environmental conditions, such as changes in oxygen availability, is likely a virulence-associated trait. Two-component systems that are regulators of gene transcription in response to environmental signals have been implicated in virulence in a number of bacterial species, including Bordetella pertussis, Salmonella enterica serovar Typhimurium, and Shigella flexneri (5,18,53). No such role has yet been demonstrated for the ArcAB system involved in oxygendependent regulation of gene ...
The structural elucidation of candicansol (I a), 3-epi-illudol (2a), and 1 -O-acetyl-3-epi-illudol (3), novel illudalane and protoilludane sesquiterpenoids isolated from cultures of Clitocybe candicans is based on a study of their 'H and 13C n.m.r. spectral data. The absolute configuration of 3-epi-illudol is also reported.
The structure of the title compounds (I)‐(VI) is confirmed by spectroscopic methods and chemical correlation.
Purpose: To detect and quantify pulmonary lesions due to pneumococcal pneumonia in a murine model by 1 H MRI. Materials and Methods:Pneumonia was induced in mice (N ϭ 5) by intranasal administration of about 1 ϫ 10 6 colony-forming units (CFU) of Streptococcus pneumonie. A group of noninfected animals (N ϭ 5) was used as a control group. MRI was performed, 48 hours after infection induction, at 4.7 T. ECG-gated gradient-echo (GRE) sequences with TE ϭ 5 msec were used. After MRI examination, the animals were sacrificed for histological examination.Results: Lungs appeared at MRI as regions with signal intensity (SI) at the level of the noise. Lesions appeared as hyperintense regions over the background and were localized mainly in the apical part of the lungs, in the medial and peribronchial regions. The anatomical localization of the lesions was confirmed by histology. The total lesion volume quantified by MRI data correlated with the total lesion volume quantified by histology. IN VIVO MRI methodologies have become established tools in the drug development process (1,2) and are particularly advantageous when used in the investigation of drug efficacy in animal models of human pathologies. We previously demonstrated that MRI allows detection and quantification of lesions in a murine model of thigh bacterial infection and that, in such animal models, MRI could replace classic microbiological methods (3). In the present study we investigated the potential usefulness of MRI in studying experimental pulmonary bacterial infections in mice. ConclusionLung parenchyma is characterized by a very low 1 H MRI signal intensity (SI), due to the low proton density of lung tissue (roughly 20% less than that of other tissues (4)) and to the peculiar microscopic arrangement of air-tissue interfaces, which produces substantial susceptibility artifacts. Motion artifacts due to cardiac and respiratory movements further contribute to decreasing the signal-to-noise ratio (SNR) of pulmonary parenchyma. These features explain why MRI is not widely used as a diagnostic tool in this anatomic district. New experimental approaches based on hyperpolarized Xe and He gases have been proposed (5,6) for lung imaging. Although extremely promising, these techniques are not widely available at present and not usable with standard instrumentation. Several techniques based on standard 1 H MRI aimed at increasing the SNR of lung parenchyma have also been proposed (7-12). However, the low SNR of lung parenchyma makes it possible to detect a number of thoracic pathologies, including pulmonary edema (13) or cancer (14), with high sensitivity.In this study we followed the hypothesis that the presence of foci of pneumonia modifies the features of pulmonary tissue, with a consequent increase in T2* and in SNR compared to normal parenchyma. In other words, instead of using pulse sequences tailored to increasing the SNR of lung parenchyma, we explored the possibility of detecting and staging pneumonia using a standard ECG-gated gradient-echo (GRE) sequence, w...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.