Hypoxia inducible factor (HIF)-1 is the key transcriptional factor involved in the adaptation process of cells and organisms to hypoxia. Recent findings suggest that HIF-1 plays also a crucial role in inflammatory and infectious diseases. Using patient skin biopsies, cell culture and murine infection models, HIF-1 activation was determined by immunohistochemistry, immunoblotting and reporter gene assays and was linked to cellular oxygen consumption. The course of a S. aureus peritonitis was determined upon pharmacological HIF-1 inhibition. Activation of HIF-1 was detectable (i) in all ex vivo in biopsies of patients suffering from skin infections, (ii) in vitro using cell culture infection models and (iii) in vivo using murine intravenous and peritoneal S. aureus infection models. HIF-1 activation by human pathogens was induced by oxygen-dependent mechanisms. Small colony variants (SCVs) of S. aureus known to cause chronic infections did not result in cellular hypoxia nor in HIF-1 activation. Pharmaceutical inhibition of HIF-1 activation resulted in increased survival rates of mice suffering from a S. aureus peritonitis. Activation of HIF-1 is a general phenomenon in infections with human pathogenic bacteria, viruses, fungi and protozoa. HIF-1-regulated pathways might be an attractive target to modulate the course of life-threatening infections.

The capacity of pathogenic microorganisms to adhere to host cells and avoid clearance by the host immune system is the initial and most decisive step leading to infections. Bacteria have developed different strategies to attach to diverse host surface structures. One important strategy is the adhesion to extracellular matrix (ECM) proteins (e.g., collagen, fibronectin, laminin) that are highly abundant in connective tissue and basement membranes. Gram-negative bacteria express variable outer membrane proteins (adhesins) to attach to the host and to initiate the process of infection. Understanding the underlying molecular mechanisms of bacterial adhesion is a prerequisite for targeting this interaction by “anti-ligands” to prevent colonization or infection of the host. Future development of such “anti-ligands” (specifically interfering with bacteria-host matrix interactions) might result in the development of a new class of anti-infective drugs for the therapy of infections caused by multidrug-resistant Gram-negative bacteria. This review summarizes our current knowledge about the manifold interactions of adhesins expressed by Gram-negative bacteria with ECM proteins and the use of this information for the generation of novel therapeutic antivirulence strategies.

Infectious diseases remain a remarkable health threat for humans and animals. In the past, the epidemiology, etiology and pathology of infectious agents affecting humans and animals have mostly been investigated in separate studies. However, it is evident, that combined approaches are needed to understand geographical distribution, transmission and infection biology of “zoonotic agents”. The genus Bartonella represents a congenial example of the synergistic benefits that can arise from such combined approaches: Bartonella spp. infect a broad variety of animals, are linked with a constantly increasing number of human diseases and are transmitted via arthropod vectors. As a result, the genus Bartonella is predestined to play a pivotal role in establishing a One Health concept combining veterinary and human medicine.

Enterococci are commensals of the intestinal tract of many animals and humans. Of the various known and still unnamed new enterococcal species, only isolates of Enterococcus faecium and Enterococcus faecalis have received increased medical and public health attention. According to textbook knowledge, the majority of infections are caused by E. faecalis. In recent decades, the number of enterococcal infections has increased, with the increase being exclusively associated with a rising number of nosocomial E. faecium infections. This increase has been accompanied by the dissemination of certain hospital-acquired strain variants and an alarming progress in the development of antibiotic resistance namely vancomycin resistance. With this review we focus on a description of the specific situation of vancomycin resistance among clinical E. faecium isolates in Germany over the past 30 years. The present review describes three VRE episodes in Germany, each of which is framed by the beginning and end of the respective decade. The first episode is specified by the first appearance of VRE in 1990 and a country-wide spread of specific vanA-type VRE strains (ST117/CT24) until the late 1990s. The second decade was initially marked by regional clusters and VRE outbreaks in hospitals in South-Western Germany in 2004 and 2005, mainly caused by vanA-type VRE of ST203. Against the background of a certain "basic level" of VRE prevalence throughout Germany, an early shift from the vanA genotype to the vanB genotype in clinical isolates already occurred at the end of the 2000s without much notice. With the beginning of the third decade in 2010, VRE rates in Germany have permanently increased, first in some federal states and soon after country-wide. Besides an increase in VRE prevalence, this decade was marked by a sharp increase in vanB-type resistance and a dominance of a few, novel strain variants like ST192 and later on ST117 (CT71, CT469) and ST80 (CT1065). The largest VRE outbreak, which involved about 2,900 patients and lasted over three years, was caused by a novel and until that time, unknown strain type of ST80/CT1013 (vanB). Across all periods, VRE outbreaks were mainly oligoclonal and strain types varied over space (hospital wards) and time. The spread of VRE strains obviously respects political borders; for instance, both vancomycin-variable enterococci which were highly prevalent in Denmark and ST796 VRE which successfully disseminated in Australia and Switzerland, were still completely absent among German hospital patients, until to date.

Background: Species of the genusBartonellaare facultative intracellular alphaproteobacteria with zoonotic potential.Bartonellainfections in humans range from mild with unspecific symptoms to life threatening, and can be transmitted via arthropod vectors or through direct contact with infected hosts, although the latter mode of transmission is rare. Among the small mammals that harbourBartonellaspp., rodents are the most speciose group and harbour the highest diversity of these parasites. Human–rodent interactions are not unlikely as many rodent species live in proximity to humans. However, a surprisingly low number of clinical cases of bartonellosis related to rodent-associatedBartonellaspp. have thus far been recorded in humans.Methods: The main purpose of this review is to determine explanatory factors for this unexpected finding, by taking a closer look at published clinical cases of bartonellosis connected with rodent-associatedBartonellaspecies, some of which have been newly described in recent years. Thus, another focus of this review are these recently proposed species.Conclusions: Worldwide, only 24 cases of bartonellosis caused by rodent-associated bartonellae have been reported in humans. Possible reasons for this low number of cases in comparison to the high prevalences ofBartonellain small mammal species are (i) a lack of awareness amongst physicians ofBartonellainfections in humans in general, and especially those caused by rodent-associated bartonellae; and (ii) a frequent lack of the sophisticated equipment required for the confirmation ofBartonellainfections in laboratories that undertake routine diagnostic testing. As regards recently describedBartonellaspp., there are presently 14 rodent-associatedCandidatustaxa. In contrast to species which have been taxonomically classified, there is no official process for the review of proposedCandidatusspecies and their names before they are published. This had led to the use of malformed names that are not based on the International Code of Nomenclature of Prokaryotes. Researchers are thus encouraged to proposeCandidatusnames to the International Committee on Systematics of Prokaryotes for approval before publishing them, and only to propose new species ofBartonellawhen the relevant datasets allow them to be clearly differentiated from known species and subspecies.Graphical