pneumoniae in diabetic mice implies that diabetes might provide a specialized environment permitting these strains to disseminate from local tissues, such as the lungs

and intestines into the blood. Although previous studies have indicated that the hyperglycemic state of diabetes provokes a functional decline of neutrophils [25, 26], phagocytosis by neutrophils from diabetic patients of K. pneumoniae 1112 was comparable to that of 1084 (data not shown). Moreover, pulmonary infections caused by K. pneumoniae 1112 and 1084 caused similar apoptosis levels of the alveolar macrophages in both diabetic and naïve mice (data not shown). Given that capsules play a pivotal role in the protection of K. pneumoniae from phagocytosis [27], it is not surprising that the well-encapsulated PF-6463922 order K. pneumoniae 1084 interacted with phagocytes in the same manner as 1112. This implied that the HV phenotype was not essential for the antiphagocytosis of K. pneumoniae. Thus, a mutant Wortmannin molecular weight library of 1084 generated using a signature-tagged mutagenesis technique is currently under in vivo screening in diabetic mice. Identification of the genetic requirement of 1084 with regard to virulence will provide insights into the means by which 1084 gains an advantage in dissemination and proliferation in the blood of diabetic mice. To our knowledge,

this is the first study using naturally-selected strains to evaluate the requirements of HV-phenotype for K. pneumoniae virulence in diabetic mice. Our findings suggest that the HV-negative strain 1084 is more virulent than the HV-positive strain 1112 under diabetic conditions, the naturally-selected strain 1084 may serve as an ideal model for identifying virulence factors, rather than relying on the HV phenotype that contributes significantly to the pathogenesis of K. pneumoniae. Conclusions HV-phenotype

is a virulent determinant for clinically isolated HV-positive K. pneumoniae. However, factors other than the HV-phenotype contribute significantly to the virulence of K. pneumoniae isolates displaying no HV-phenotype, particularly for systemic dissemination under diabetic conditions. else Methods Bacterial isolates During a fifteen-month period from April 2002, a total of 473 non-repetitive K. pneumoniae were isolated from the infection foci of patients who had K. pneumoniae -related infections treated at a referral medical center in JSH-23 molecular weight central Taiwan. The clinical isolates, which were confirmed as K. pneumoniae using the API 20E system (BioMerieux), were collected from various infection foci: 11.6% were from blood; 4%, from liver aspirates; 0.4%, from eye aspirates; 0.8%, from cerebrospinal fluid; 26.2%, from non-hepatic abscesses; 22.8%, from sputum; 8.5%, from wound pus; and 25.6%, from other body fluids. Due to the difficulty in determining whether K. pneumoniae is the primary pathogen in a urinary tract infection, urine isolates were excluded.