Dangerous Human Pathogen Research Articles

A Novel Class of Cysteine Protease Inhibitors: Solution Structure of Staphostatin A from Staphylococcus aureus

A series of secreted proteases are included among the virulence factors documented for Staphylococcus aureus. In light of increasing antibiotic resistance of this dangerous human pathogen, these proteases are considered as suitable targets for the development of novel therapeutic strategies. The recent discovery of staphostatins, endogenous, highly specific, staphylococcal cysteine protease inhibitors, opened a possibility for structure-based design of low molecular weight analogues. Moreover, the crystal structure of staphostatin B revealed a distinct folding pattern and an unexpected, substrate-like binding mode. The solution structure of staphostatin A reported here confirms that staphostatins constitute a novel, distinct class of cysteine protease inhibitors. In addition, the structure knowledge-based mutagenesis studies shed light on individual structural features of staphostatin A, the inhibition mechanism, and the determinants of distinct specificity of staphostatins toward their target proteases.

Siderophores of the human pathogenic fluorescent pseudomonads.

Bacteria need a sufficient supply of iron in ionic form for their metabolism. When living in an environment where this is not possible (as in the soil due to the presence of highly unsoluble ferric oxide hydrates, or in living organisms where iron is bound to peptidic chelators) Fe3+ complexing compounds, called siderophores, are produced. The siderophores of Pseudomonas aeruginosa, a dangerous opportunistic human pathogen, and of related potentially pathogenic species will be presented.

Immunization of BALB/c mice against Helicobacter felis infection with Helicobacter pylori urease

Background/Aims: Because Helicobacter pylori is a potentially dangerous human pathogen, the protective potential of oral immunization with H. pylori urease and its subunits was evaluated in an animal model. Methods: Mice were orally immunized with H. pylori sonicate, urease, or recombinant enzymatically inactive urease subunits and then challenged with Helicobacter felis. Control mice were sham-immunized. Results: H. felis colonization was present 5 days after challenge in 9 of 10 sham-immunized, 6 of 9 sonicate-immunized, and 3 of 10 urease-immunized animals (P = 0.031 vs. sham-immunized). Twelve days after challenge, urease B-immunized mice had a weaker colonization than sham-immunized controls, whereas urease A had no effect. After 70 days, most urease A- and urease B-immunized mice had cleared the colonization (10/17: P = 0.0019; 16/20: P = 0.00002 vs. sham-immunized). In urease B-immunized animals, protection was often associated with corpus gastritis. Conclusions: Oral immunization with H. pylori urease protects mice against H. felis infection. Enzymatically inactive urease A and B subunits contain protective epitopes. It is unclear whether protection depends on the development of a mononuclear inflammatory response in the gastric corpus. Our observations should encourage the development of a human vaccine.

PREDICTING FILM PACKAGING NEEDS FOR LIGHTLY PROCESSED FRUITS AND VEGETABLES

Packaging films are currently used to modify the environment surrounding most lightly processed fruits and vegetables. For some produce, it has been demonstrated that low O2 and/or elevated CO2 will maintain quality and extend shelf life. For others, reduction of water loss may be of more importance. We have developed a model which can be used to design packages for concurrent modification of both O2 and H2O. The effect of variation in respiration from one batch of product to another on resultant O2 levels in packages will be discussed in relation to the risk associated with excessively low levels of package O2. Such low levels of O2 not only impair the quality of the product but provide a favorable environment for development of dangerous human pathogens. There is also risk associated with inadvertent increases in temperature during handling and marketing. For environmental considerations, it is desirable to use films which can be reused and/or recycled. The impact of these variables on the prediction of appropriate films and designs for packaging will be discussed.

MODELING DISTRIBUTION OF STEADY-STATE O2 LEVELS IN MODIFIED ATMOSPHERE PACKAGES: AN APPROACH FOR DESIGNING SAFE PACKAGES

Steady-state O2 levels in modified atmosphere (MA) packages of fruits or vegetables may vary from target O2 levels due to variation in O2 uptake and film permeability. Successful MA package systems must be designed such that variation in O2 uptake will not cause undesirable changes to product quality. Such changes could include fermentation and off-flavor development as well as growth of dangerous human pathogens. A computer model was developed to predict the distribution of package O2 levels for a product of any given O2 uptake characteristics including the coefficient of variation. The model was used to predict appropriate target O2 levels for any commodity given a lower O2 limit for safe storage and the percent of packages which can be tolerated at unsafe levels. For instance, if it is tolerable to have 1 in 1000 MA packages of cut broccoli reach less than 0.5 kPa O2 at steady-state, the model predicts that the appropriate target O2 at 0C should be about 1.75 kPa if the coefficient of variation of O2 uptake is 10%. Empirical support for the model will be presented.