Invasive candidiasis is associated with high morbidity and mortality. Clinical diagnosis is complicated by a lack of specific clinical signs and symptoms of disease. Laboratory diagnosis is also complex because circulating antibodies to Candida species may occur in normal individuals as the result of commensal colonization of mucosal surfaces thereby reducing the usefulness of antibody detection for the diagnosis of this disease. In addition, Candida species antigens are often rapidly cleared from the circulation so that antigen detection tests often lack the desired level of sensitivity. Microbiological confirmation is difficult because blood cultures can be negative in up to 50% of autopsy-proven cases of deep-seated candidiasis or may only become positive late in the infection. Positive cultures from urine or mucosal surfaces do not necessarily indicate invasive disease although can occur during systemic infection. Furthermore, differences in the virulence and in the susceptibility of the various Candida species to antifungal drugs make identification to the species level important for clinical management. Newer molecular biological tests have generated interest but are not yet standardized or readily available in most clinical laboratory settings nor have they been validated in large clinical trials. Laboratory surveillance of at-risk patients could result in earlier initiation of antifungal therapy if sensitive and specific diagnostic tests, which are also cost effective, become available. This review will compare diagnostic tests currently in use as well as those under development by describing their assets and limitations for the diagnosis of invasive candidiasis.

An early step in the pathogenesis of non-typhoidal Salmonella species is the ability to penetrate the intestinal epithelial monolayer. This process of cell invasion requires the production and transport of secreted effector proteins by a type III secretion apparatus encoded in Salmonella pathogenicity island I (SPI-1). The control of invasion involves a number of genetic regulators and environmental stimuli in complex relationships. SPI-1 itself encodes several transcriptional regulators (HilA, HilD, HilC, and InvF) with overlapping sets of target genes. These regulators are, in turn, controlled by both positive and regulators outside SPI-1, including the two-component regulators BarA/SirA and PhoP/Q, and the csr post-transcriptional control system. Additionally, several environmental conditions are known to regulate invasion, including pH, osmolarity, oxygen tension, bile, $Mg^{2+}$ concentration, and short chain fatty acids. This review will discuss the current understanding of invasion control, with emphasis on the interaction of environmental factors with genetic regulators that leads to productive infection.

It had long been assumed that a bacterial cell was dead when it was no longer able to grow on routine culture media. We now know that this assumption is simplistic, and that there are many situations where a cell loses culturability but remains viable and potentially able to regrow. This mini-review defines what the 'viable but nonculturable' (VBNC) state is, and illustrates the methods that can be used to show that a bacterial cell is in this physiological state. The diverse environmental factors which induce this state, and the variety of bacteria which have been shown to enter into the VBNC state, are listed. In recent years, a great amount of research has revealed what occurs in cells as they enter and exist in this state, and these studies are also detailed. The ability of cells to resuscitate from the VBNC state and return to an actively metabolizing and culturable form is described, as well as the ability of these cells to retain virulence. Finally, the question of why cells become nonculturable is addressed. It is hoped that this mini-review will encourage researchers to consider this survival state in their studies as an alternative to the conclusion that a lack of culturability indicates the cells they are examining are dead.

To gain maximal benefit in a competitive environment, single-celled bacteria have adopted a community genetic regulatory mechanism, known as quorum sensing (QS). Many bacteria use QS signaling systems to synchronize target gene expression and coordinate biological activities among a local population. N-acylhomoserine lactones (AHLs) are one family of the well-characterized QS signals in Gram-negative bacteria, which regulate a range of important biological functions, including virulence and biofilm formation. Several groups of AHL-degradation enzymes have recently been identified in a range of living organisms, including bacteria and eukaryotes. Expression of these enzymes in AHL-dependent pathogens and transgenic plants efficiently quenches the microbial QS signaling and blocks pathogenic infections. Discovery of these novel quorum quenching enzymes has not only provided a promising means to control bacterial infections, but also presents new challenges to investigate their roles in host organisms and their potential impacts on ecosystems.

Salmonella enterica serovar Typhimurium causes human gastroenteritis and a systemic typhoid-like infection in mice. A critical virulence determinant of Salmonella is the ability to invade mammalian cells. The expression of genes required for invasion is tightly regulated by environmental conditions and a variety of regulatory genes. The hilA regulator encodes an OmpR/ToxR family transcriptional regulator that activates the expression of invasion genes in response to both environmental and genetic regulatory factors. Work from several laboratories has highlighted that regulation of hilA expression is a key point for controlling expression of the invasive phenotype. A number of positive regulators of hilA expression have been identified including csrAB, sirA/barA, pstS, hilC/sirC/sprA, fis, and hilD. HilD, an AraC/XylS type transcriptional regulator, is of particular importance as a mutation in hilD results in a 14-fold decrease in chromosomal hilA::Tn5lacZY-080 expression and a 53-fold decrease in invasion of HEp-2 cells. It is believed that HilD directly regulates hilA expression as it has been shown to bind to hilA promoter sequences. In addition, our research group, and others, have identified genes (hilE, hha, pag, and lon) that negatively affect hilA transcription. HilE appears to be an important Salmonella-specific regulator that plays a critical role in inactivating hilA expression. Recent work in our lab has been directed at understanding how environmental signals that affect hilA expression may be processed through a hilE pathway to modulate expression of hilA and the invasive phenotype. The current understanding of this complex regulatory system is reviewed.

Vibrio vulnificus is an opportunistic pathogen of humans that has the capability of causing rare, yet devastating disease. The bacteria are naturally present in estuarine environments and frequently contaminate seafoods. Within days of consuming uncooked, contaminated seafood, predisposed individuals can succumb to sepsis. Additionally, in otherwise healthy people, V. vulnificus causes wound infection that can require amputation or lead to sepsis. These diseases share the characteristics that the bacteria multiply extremely rapidly in host tissues and cause extensive damage. Despite the analysis of virulence for over 20 years using a combination of animal and cell culture models, surprisingly little is known about the mechanisms by which V. vulnificus causes disease. This is in part because of differences observed using animal models that involve infection with bacteria versus injection of toxins. However, the increasing use of genetic analysis coupled with detailed animal models is revealing new insight into the pathogenesis of V. vulnificus disease.