Characterization of the L-form switch in the Gram-negative pathogen Streptobacillus moniliformis.

Almost all major classes of bacteria are surrounded by a peptidoglycan cell wall, which is a crucial target for antibiotics. It is now understood that many bacteria can tolerate loss of the cell wall provided that they are in an isotonic environment. Furthermore, in some cases the cells can continue to proliferate in a state known as the L-form. L-form proliferation occurs by an unusual blebbing or tubulation mechanism that is completely independent of the normally essential division machine or cell wall synthetic enzymes, and is resistant to cell wall-active antibiotics. However, the growth is limited by reactive oxygen species generated by the respiratory chain pathway. In this work, we examined the walled to L-form transition in a pathogenic Gram-negative bacterium, Streptobacillus moniliformis, which naturally lacks the respiratory chain pathway, under aerobic conditions. L-form-like cells often emerged spontaneously, but proliferation was not observed unless the cells were treated with cell wall-active antibiotics. Time-lapse imaging revealed that cell division of S. moniliformis L-forms involves unusual membrane dynamics with an apparent imbalance between outer membrane and cytoplasmic volume growth. The results suggest that outer membrane expansion may be an important general factor for L-form proliferation of diderm bacteria.

A bacterial ABC transporter enables import of mammalian host glycosaminoglycans.

Glycosaminoglycans (GAGs), such as hyaluronan, chondroitin sulfate, and heparin, constitute mammalian extracellular matrices. The uronate and amino sugar residues in hyaluronan and chondroitin sulfate are linked by 1,3-glycoside bond, while heparin contains 1,4-glycoside bond. Some bacteria target GAGs as means of establishing colonization and/or infection, and bacterial degradation mechanisms of GAGs have been well characterized. However, little is known about the bacterial import of GAGs. Here, we show a GAG import system, comprised of a solute-binding protein (Smon0123)-dependent ATP-binding cassette (ABC) transporter, in the pathogenic Streptobacillus moniliformis. A genetic cluster responsible for depolymerization, degradation, and metabolism of GAGs as well as the ABC transporter system was found in the S. moniliformis genome. This bacterium degraded hyaluronan and chondroitin sulfate with an expression of the genetic cluster, while heparin repressed the bacterial growth. The purified recombinant Smon0123 exhibited an affinity with disaccharides generated from hyaluronan and chondroitin sulfate. X-ray crystallography indicated binding mode of Smon0123 to GAG disaccharides. The purified recombinant ABC transporter as a tetramer (Smon0121-Smon0122/Smon0120-Smon0120) reconstructed in liposomes enhanced its ATPase activity in the presence of Smon0123 and GAG disaccharides. This is the first report that has molecularly depicted a bacterial import system of both sulfated and non-sulfated GAGs.

Oh rats! Fever, rash and arthritis in a young woman.

A 17-year-old girl presented with worsening right-sided hip and low back pain for 2 days. She had also experienced intermittent fevers and a recurring maculopapular rash over the past 2 weeks. Social history revealed the presence of three domestic rats living in the girl's home. Blood cultures returned positive for Streptobacillus moniliformis, the causative agent of rat-bite fever. Rat-bite fever often goes undiagnosed, as the clinical presentation is non-specific. Untreated, the infection can result in death due to sepsis or endocarditis. The bacterium is generally susceptible to penicillin antibiotics with full clinical recovery when treated in a timely and appropriate manner. After 4 weeks of intravenous antibiotics, our patient fully recovered without long-term sequelae.

Bacteria isolated from conspecific bite wounds in Norway and black rats: implications for rat bite-associated infections in people.

Bites associated with wild and domestic Norway and black rats (Rattus norvegicus and Rattus rattus) may have a variety of health consequences in people. Bite-related infections are among the most significant of these consequences; however, there is little data on the infectious agents that can be transmitted from rats to people through biting. This is problematic because without an accurate understanding of bite-related infection risks, it is difficult for health professionals to evaluate the adequacy of existing guidelines for empirical therapy. The objectives of this study were to increase our knowledge of the bacterial species associated with rat bites by studying bite wounds that wild rats inflict upon one another and to review the literature regarding rat bites and bite wound management. Wild Norway and black rats (n=725) were trapped in Vancouver, Canada, and examined for bite wounds in the skin. All apparently infected wounds underwent aerobic and anaerobic culture, and isolated bacteria were identified. Thirty-six rats had bite wound-related infections, and approximately 22 different species of bacteria belonging to 18 genera were identified. Staphylococcus aureus was the most common isolate; however, the majority of infections (72.5%) were polymicrobial. Rat bites can result in infection with a number of aerobic and anaerobic Gram-positive and Gram-negative bacteria. In humans, these wounds are best managed through early recognition and cleansing. The benefit of prophylactic antimicrobial treatment is debatable, but given the deep puncturing nature of rodent bites, we suggest that they should be considered a high risk for infection. Antibiotics selected should include coverage for a broad range of bacterial species.

Rat bite fever and Streptobacillus moniliformis.

Rat bite fever, caused by Streptobacillus moniliformis, is a systemic illness classically characterized by fever, rigors, and polyarthralgias. If left untreated, it carries a mortality rate of 10%. Unfortunately, its nonspecific initial presentation combined with difficulties in culturing its causative organism produces a significant risk of delay or failure in diagnosis. The increasing popularity of rats and other rodents as pets, together with the risk of invasive or fatal disease, demands increased attention to rat bite fever as a potential diagnosis. The clinical and biological features of rat bite fever and Streptobacillus moniliformis are reviewed, providing some distinguishing features to assist the clinician and microbiologist in diagnosis.

Bacteremia by Streptobacillus moniliformis: first case described in Spain.

Described here is the case of an 87-year-old man who developed fever, chills and discomfort caused by Streptobacillus moniliformis. This pathogen is one of the causes of rat-bite fever, an uncommon bacterial illness transmitted through a bite or scratch from a rodent or the ingestion of food or water contaminated with rat faeces. Cases of rat-bite fever are rarely reported in Spain. The patient reported no history of rat bite or rodent contact, and the only known risk factor was contact with a dog and a cat that were kept as pets. Streptobacillus moniliformis was isolated in two sets of blood cultures. This case represents what is believed to be the first report of bacteremia due to Streptobacillus moniliformis in Spain.

Streptobacillus moniliformis--a zoonotic pathogen. Taxonomic considerations, host species, diagnosis, therapy, geographical distribution.

Streptobacillus moniliformis (Sm), the causative agent of rat-bite fever and Haverhill fever in man, is also a pathogen in certain laboratory and domestic animals. With the introduction of modern maintenance systems, this microorganism seemed to be eradicated from laboratory animal units, but recent reports of Streptobacillus moniliformis (Sm) in colonies of laboratory rodents give evidence that this 'forgotten' bacterium can still be found even behind hygienic barrier systems. Although various national and international recommendations on microbiological screening include Sm, attempts to screen might fail because of insufficient knowledge about this remarkable bacterium. This article highlights these problems. As there is no recent review of Streptobacillus moniliformis, present knowledge of this zoonotic agent is summarized to include: description of the bacterium, its taxonomic position, host spectrum and clinical importance for animals and man, cultivation, diagnosis, antibiotic therapy, risk to laboratory personnel (occupational hazard) and geographical distribution.

Comparison of media with and without 'Panmede' for the isolation of Streptobacillus moniliformis from blood cultures and observations on the inhibitory effect of sodium polyanethol sulphonate.

Fastidious anaerobe broth and brain-heart infusion cysteine broth supplemented with 'Panmede' (a papain digest of ox liver) 2.5% supported the recovery of five Streptobacillus moniliformis strains from simulated blood cultures. Other media tested in parallel--brain heart infusion cysteine broth without 'Panmede' and Brewer's thioglycollate broth--were unreliable. Sodium polyanethol sulphonate (Liquoid) 0.05%, inhibited five isolates of S. moniliformis, including isolates from patients with Haverhill Fever. Occasionally, Liquoid 0.025% was also inhibitory and a heavy inoculum of one strain, NCTC11194, was completely inhibited by Liquoid 0.012% in simulated nutrient-broth blood cultures. These results suggest that the choice of media included in each blood-culture set is critical for the optimal isolation of S. moniliformis. Brain-heart infusion cysteine broth supplemented with 'Panmede', or commercially available fastidious anaerobe broth, without Liquoid, is recommended.

Host-parasite relationships in experimental Streptobacillus moniliformis arthritis in mice.

Several variables of host and parasite, relating to the establishment of the chronic Streptobacillus moniliformis-induced arthritis, were studied. Results from these studies indicated (i) that intravenous inoculation of the organism produced a progressive bacteremia and a polyarthritis, whereas subcutaneous inoculation into the top of the back foot produced an intermittent bacteremia and arthritis only in that foot, (ii) that serum-broth-grown cells were more virulent than serum-agar-grown cells, (iii) that young animals were more susceptible to infection than old, and (iv) that the organism apparently had a predilection for joints. It was also determined that the leukocyte and antibody responses of mice to infection were minimal with a slight neutrophilia and a maximum antibody titer of 1:640 detected after infection. Measurements of the effectiveness of antibody and leukocytes in prevention or resolution of infection indicated (i) that the presence of homologous antibody prior to infection prolonged the incubation period for development of the lesion, (ii) that the opsonic index was 1.2 to 1.4, and (iii) that the organism was apparently resistant to destruction by in vitro phagocytosis and actually increased in number in the presence of phagocytes. It was concluded that these represented some of the prime factors contributing to the establishment of the infection and its chronicity.

Cholesterol requirement of mycoplasmas.

Cholesterol requirement for growth of mycoplasmas was tested in a serum-free medium supplemented with albumin, l-arginine, palmitic acid, and various concentrations of cholesterol dissolved in Tween 80. In cases in which Tween 80 was shown to inhibit growth, the test medium was supplemented with cholesterol dissolved in ethanol. Of the 31 species examined, all but Mycoplasma laidlawii, M. granularum, and Mycoplasma species strain S-743 exhibited a growth response to cholesterol. No requirement for cholesterol could be shown with the stable L-phase variants of Streptobacillus moniliformis and Proteus species. The results provide experimental support for the view that the large majority of the established Mycoplasma species require cholesterol for growth.