Experimental Infection Of Rabbits Research Articles

Treponema pallidum subsp. pallidum strains DAL-1 and Philadelphia 1 differ in generation times in vitro as well as during experimental rabbit infection.

In this work, we determined that Treponema pallidum subsp. pallidum (TPA) DAL-1 (belonging to Nichols-like group of TPA strains) grew 1.53 (± 0.08) times faster compared to TPA Philadelphia 1 (SS14-like group) during in vitro cultivations. In longitudinal individual propagation in rabbit testes (n = 12, each TPA strain), infection with DAL-1 manifested clinical symptoms (induration, swelling, and erythema of testes) sooner than Philadelphia 1 infection, which resulted in a significantly shorter period of the experimental passages for DAL-1 (median = 15.0 and 23.5 days, respectively; p < 0.01). To minimize the confounding conditions during rabbit experiments, the growth characteristics of DAL-1 and Philadelphia 1 strains were determined during TPA co-infection of rabbit testes (n = 20, including controls). During two weeks of intratesticular co-infection, DAL-1 overgrew Philadelphia 1 in all twelve testes, regardless of inoculation ratio and dose (median of relative excess DAL-1 multiplication = 84.85×). Moreover, higher DAL-1 to Philadelphia 1 inoculum ratios appeared to increase differences in growth rates, suggesting direct competition between strains for available nutrients during co-infection. These experiments indicate important physiological differences between the two TPA strains and suggest growth differences between Nichols-like and SS14-like strains that are potentially linked to their virulence and pathogenicity.

Dynamics of morphofunctional parameters in experimental pseudomonosis of rabbits

Among the most frequently reported diseases of rabbits, the main place is occupied by diseases of bacterial etiology, the pathogens of which are characterized by multidrug resistance. The aim of the study was to analyze the dynamics of morphometric indicators during experimental infection of rabbits with Pseudomonas aeruginosa bacteria. When assessing colonization resistance of organs, the following indicators were taken into account: colonization index, ratio of the number of microorganisms isolated from nasal cavity washes, contents of cecum of clinically healthy and sick animals. Significant changes in morphological parameters (p 0.05) were revealed during the isolation of P. aeruginosa from blood, lymph nodes, spleen, liver, and kidneys of sick rabbits. Overgrowth of isolates producing adhesive antigens, hemolysins, bacteriocins should be considered as prognostic markers of connective tissue dysplasia. The initiation, development, and outcome of microbial overgrowth syndrome are mediated by morphofunctional changes in compensatory mechanisms of mucociliary clearance system and colonization resistance.

Clonal isolates of Treponema pallidum subsp. pallidum Nichols provide evidence for the occurrence of microevolution during experimental rabbit infection and in vitro culture.

The recent development of a system for long-term in vitro culture of the syphilis spirochete, Treponema pallidum subsp. pallidum, has introduced the possibility of detailed genetic analysis of this bacterium. In this study, the in vitro culture system was used to isolate and characterize clonal populations of T. pallidum subsp. pallidum Nichols, the most widely studied strain. In limiting dilutions experiments, it was possible to establish cultures with inocula as low as 0.5 T. pallidum per well despite the long generation time (~35 to 40 hours) of this organism. Six Nichols strain clones isolated by limiting dilution were characterized in detail. All clones exhibited indistinguishable morphology and motility, highly similar in vitro multiplication rates, and comparable infectivity in the rabbit model (ID50 ≤ 100 bacteria). Genomic sequencing revealed sequence heterogeneity in the form of insertions or deletions at 5 sites, single nucleotide variations at 20 sites, and polynucleotide (polyG/C) tract length differences at 22 locations. Genomic sequences of the uncloned Nichols strain preparations propagated in rabbits or in vitro cultures exhibited substantial heterogeneity at these locations, indicating coexistence of many varied 'clonotypes' within these populations. Nearly all genetic variations were specific for the Nichols strain and were not detected in the >280 T. pallidum genomic sequences that are currently available. We hypothesize that these Nichols strain-specific sequence variations arose independently either during human infection or within the 110 years since the strain's initial isolation, and thus represent examples of microevolution and divergence.

DIARRHEA SYNDROME CAUSED BY CAMPYLOBACTER JEJUNI IN CALVES

ABSTRACT Campylobacter jejuni(C.jejuni) is the leading bacterial cause of food born diarrheal illness and enterocolitis worldwide in human and young animals. A total of 140 samples (100 fecal samples of calves and 40 raw milk samples of cow) were collected from Dakahlia governorate dairy farms for isolation and identification of C.jejuni by using cultural, biochemical, molecular methods and detection of the virulent cadF gene using PCR. Moreover, the isolated C.jejuni subjected for antimicrobial susceptibility test. Then, we develop an experimental infection of rabbits by inoculation with 1 × 109 colony-forming units (cfu) of completely identified C.jejuni. Rabbits divided into 3 groups: infected untreated (G1), infected treated with enrofloxacine (G2), control (G3) to study pathogenesis, fecal inflammatory response, histopthology, immunohistochemistry and ultrastructural changes post inoculation in the three groups. Results revealed that, from 140 fecal and raw milk samples only 41 isolates were bacteriologically and biochemically identified as Campylobacter spp . Seven isolated strains were positively amplified for map A gene specific to C.jejuni and carried the cadF virulence gene. C.jejuniisolateswere resistant to amoxicillin and ampicillin and highly susceptible to norfloxacine and erythromycin.After oral infection with C. jejuni90% of rabbits developed diarrheawith highly fecal inflammatory responses in G1, but mild in G2(treated) and negative in G3(control). Pronounced histopathologic changes were investigated in G1 during the acute phase (days 1 to 3) restricted on distal small intestine and colon including massive destruction of villi and loss of intestinal glands.The submucosa and muscularis mucosa showed the presence of edema with congested blood vessels, while hemorrhage was seen in the muscularispropria layer. The changes were mild and involved only the villi in treated group (G2), while abscent in control (G3). These results were confirmed by immunostaining, suggesting that C.jejuni is capable of invading deep intestinal tissues down to the submucosal layer in G1 while in G2 infection, the reaction was confined mainly to the villi, and was greatly reduced in the submucosa. Electronmicroscope showed all stages of invasion and associating damages from postinfection, colonizationa and villus damage. Thereby, the implementation of hyagenic practices during milking and proper handling of milk during calves feeding with regular monitoring of antibiogram profile are very crucial in preventing C.jejuni infection, colonization and intestinal damage and subsequently economic loss in dairy farm.

Clinicopathological and Hematological Changes in Consequence to Experimental Infection of Rabbits with Pasteurella Multocida Type A

The current research aimed to study clinical, hematological and pathological changes occurred due to experimentally challenged rabbits with Pasteurella multocida type A. Twelve healthy Pasteurella multocida free rabbits were divided into control and challenged groups. Rabbits of the challenged group were intra-nasally inoculated with 0.5 ml of 1x105 CFU of Pasteurella multocida type A, while rabbits of the control group were inoculated with 0.5 ml of brain heart infusion broth (BHI). Clinical signs, hematological parameters and histopathological lesions were recoded for 14 days. Rabbits of challenged group showed nasal rubbing with minimal mucus discharge, conjunctivitis and reduction in spontaneous activity, but no mortality occurred. Hematologically, there was highly significant low RBCs count with concomitant significantly reduction of PCV in challenged rabbits, but hemoglobin concentration was insignificantly low in challenged animals as compared to control. Although, there was insignificant increase of WBCs count in challenged group, neutrophils and monocytes recorded significant and highly significant high value in challenged rabbits than control, respectively. Challenged rabbits, however demonstrated highly significant lymphopenia, but other blood parameters did not show any significant differences between challenged and control rabbits. Histopathologically, challenged animals showed meningitis, congestion and degenerative changes in respiratory epithelium, bronchopneumonia, vacuolar degeneration of hepatocytes and vascular changes in heart and spleen. Conclusively, the current study verified that challenging rabbits with Pasteurella multocida serotype A was not lethal and although it was essentially pneumotropic in nature, it caused lesions in other visceral organs, which in absence of bacteremia, could be caused by bacterial endotoxin liberated during disease pathogenesis.

Different susceptibility and pathogenesis of rabbit genotype 3 hepatitis E virus (HEV-3) and human HEV-3 (JRC-HE3) in SPF rabbits

Hepatitis E virus (HEV) is an increasingly important zoonotic infection in humans with HEV genotypes 3 and 4 being recognized as zoonotic pathogens. The relatively recently isolated genotype 3 rabbit HEV (rHEV-3) and the more well known genotype 3 isolates from humans and swine (hsHEV-3) have all been confirmed experimentally to be capable of infecting both non-human primates and specific-pathogen free (SPF) pigs. In a previous study rHEV-3 was shown to cause acute hepatitis in experimentally infected rabbits. However, whether hsHEV-3 can productively infect rabbits remained unclear. The objective of this study was to investigate the experimental infection of rabbits with human HEV-3 (hHEV-3, JRC-HE3), to compare it to that with rHEV-3 (CHN-BJ-rb14) and to further characterise the pathogenesis of the two isolates. All animals inoculated with rHEV-3 (CHN-BJ-rb14) became infected, exhibiting an intermittent viremia, elevated liver enzymes, and persistent fecal virus shedding throughout the 15 week study period. Liver histopathology showed acute inflammation and both positive- and negative-stranded viral RNA was detected in various tissues from necropsied rabbits. By contrast, neither sero-conversion nor alanine aminotransferase (ALT) elevation was observed in most rabbits inoculated with hHEV-3 (JRC-HE3). In addition, rHEV-3 (CHN-BJ-rb14) but not hHEV-3 (JRC-HE3) recovered from primary infected rabbits was transmissible to naive rabbits. These results showed that SPF rabbits are readily susceptible to infection with rHEV-3 (CHN-BJ-rb14) but not hHEV-3 (JRC-HE3), which might indicate the influence of viral genomic organization on its pathogenicity.

Blood tumour necrosis factor-α and the pathogenesis of anaemia in &lt;i&gt;Trypanosoma brucei&lt;/i&gt; infected rabbits

Trypanosomosis is a protozoan infection of domestic and wild animals characterized by anaemia, however, the pathogenesis of trypanosomosis-induced anaemia is not fully understood. This study evaluated the possible roles of Tumour Necrosis Factor-alpha (TNF-α) in the pathogenesis of anaemia induced by Trypanosoma brucei in rabbits. Twelve adult rabbits of both sexes with mean weight of 2.1 ± 0.1kg were randomly assigned into two groups of six rabbits each. Group A rabbits were intraperitoneally (i.p) infected with blood containing 2 x 106/ml of T. brucei , while group B (control) rabbits were injected with one ml of normal saline i.p. Blood was collected from the ear vein before infection and weekly thereafter for six weeks post-infection (p.i), in order to determine the packed cell volume (PCV), haemoglobin (Hb) concentration, red blood cell (RBC) count, reticulocyte count (RC) and serum concentrations of TNF-α. The PCV, RBC count and Hb concentration were significantly (p<0.05) lower in group A than group B rabbits throughout the duration of the study. Serum concentration of TNF-α was significantly (p<0.05) higher in group A (227.5 ± 8.1 ng/ml) than group B (51.3 ± 8.2 ng/ml) at week four post-infection. The serum concentration of TNF-α negatively correlated with PCV (r=-0.513) and Hb (r=-0.769) in group A. The study concluded that anaemia observed during experimental infection in rabbits with trypanosomosis was associated with increased levels of TNF-α. Keywords : Anaemia, Rabbits, Pathogenesis, Trypanosomosis, Tumour Necrosis Factor-α

Diagnosis of Sheep Trichostrongylosis Based on Imune Response Profile in Experimental Rabbit Infection

Diagnosis of Sheep Trichostrongylosis Based on Imune Response Profile in Experimental Rabbit Infection

Experimental infections of rabbits with proliferative and latent stages of Besnoitia besnoiti

Experimental infections of rabbits with proliferative and latent stages of Besnoitia besnoiti

Experimental infections of rabbits with proliferative and latent stages of Besnoitia besnoiti.

Cattle besnoitiosis due to Besnoitia besnoiti is spreading across Europe and is responsible for severe economic losses in newly infected herds. Experimentally speaking, rabbits have been found to be susceptible to this parasite. The adaptation of B. besnoiti to rabbits may offer a new, easier and cheaper model of investigation for this disease. This study compared the virulence between tachyzoites and bradyzoites of B. besnoiti in rabbits. Eighteen New Zealand rabbits were allocated into three groups of six animals each. The rabbits from the control (group C), “tachyzoite” (group T) and “bradyzoite” (group B) groups were subcutaneously injected in the right flank with 66 μg of ovalbumin, 6.106 tachyzoites (125th passage on Vero cells) and 6.106 bradyzoites (collected from a natural infected cow) of B. besnoiti, respectively. Clinical follow-up and blood sampling for serological survey and qPCR were performed during 10 weeks until euthanasia. Molecular and immunohistochemistry examination was achieved on 25 samples of tissue per rabbit. Seroconversion occurred in group T without any clinical signs. Rabbits of group B exhibited a febrile condition (temperature above 40 °C from day 8 to day 11 following injection) with positive qPCR in blood. Cysts of B. besnoiti were found on skin samples and organs of rabbits from group B in tissue explored with threshold cycle (Ct) values below 30. These results suggest a higher virulence of bradyzoites in rabbits than Vero cell-cultivated tachyzoites. The proposed model could be used to assess the in vivo effectiveness of vaccine or drugs against cattle besnoitiosis.

Experimental infection of rabbits with bovine viral diarrhoea virus by a natural route of exposure

Bovine viral diarrhoea virus (BVDV) is an important pathogen of cattle that can naturally infect a wide range of even-toed ungulates. Non-bovine hosts may represent reservoirs for the virus that have the potential to hamper BVDV eradication programs usually focused on cattle. Rabbits are very abundant in countries such as the United Kingdom or Australia and are often living on or near livestock pastures. Earlier reports indicated that rabbits can propagate BVDV upon intravenous exposure and that natural infection of rabbits with BVDV may occur but experimental proof of infection of rabbits by a natural route is lacking. Therefore, New Zealand White rabbits were exposed to a Scottish BVDV field strain intravenously, oro-nasally and by contaminating their hay with virus. None of the animals showed any clinical signs. However, the lymphoid organs from animals sacrificed at day five after exposure showed histological changes typical of transient infection with pestivirus. Most organ samples and some buffy coat samples were virus positive at day five but saliva samples remained negative. Development of antibodies was observed in all intravenously challenged animals, in all of the nebulised group and in four of six animals exposed to contaminated hay. To our knowledge this is the first report of BVDV propagation in a species other than ruminants or pigs after exposure to the virus by a natural route. However, to assess the role of rabbits as a potential reservoir for BVDV it remains to be determined whether persistent infection caused by intra-uterine infection is possible and whether BVDV is circulating in wild rabbit populations.

The European Rabbit (Oryctolagus cuniculus), a Source of Zoonotic Cryptosporidiosis

Cryptosporidium spp. have been found in the faeces of over 150 mammalian host species, but the risks to public health from wildlife are poorly understood. In summer 2008, the Cryptosporidium sp. rabbit genotype was identified as the aetiological agent in an outbreak of waterborne human cryptosporidiosis. The source was a wild rabbit that had entered a treated water tank. To establish current knowledge about Cryptosporidium spp. infecting lagomorphs, especially the host range and biological characteristics of the rabbit genotype, and the potential risks to public health that rabbits may pose in the transmission of zoonotic cryptosporidiosis, we undertook a literature and data review. The literature returned demonstrates that although the European rabbit (Oryctolagus cuniculus) has been the most widely studied lagomorph, few large scale studies were found. The prevalence of Cryptosporidium spp. in wild rabbit populations in the two large scale studies was 0.9% (95%CI 0.2-5.0) and 0.0% (95%CI 0.0-1.6). Neither study provided age nor sex profiles nor typing of Cryptosporidium isolates. The infecting Cryptosporidium species was confirmed in just four other studies of rabbits, all of which showed the rabbit genotype. Human-infectious Cryptosporidium species including Cryptosporidium parvum have caused experimental infections in rabbits and it is likely that this may also occur naturally. No published studies of the host range and biological features of the Cryptosporidium rabbit genotype were identified, but information was generated on the identification and differentiation of the rabbit genotype at various genetic loci. Both pet and wild rabbits are a potential source of human cryptosporidiosis and as such, good hygiene practices are recommended during and after handling rabbits or exposure to their faeces, or potentially contaminated surfaces. Water supplies should be protected against access by wildlife, including rabbits.

Effects of antibiotics on phagocytosis of polymorphonuclear leukocytes in experimental rabbit infection models

Effects of antibiotics on phagocytosis of polymorphonuclear leukocytes in experimental rabbit infection models

Epizootiology of lumpy skin disease outbreak in cattle in middle of Egypt, 2006

The current investigation studied an outbreak of lumpy skin disease of cattle in Beni-Suef and Al-Fayium governorates from March up to September 2006. Epidemiological data over a total of 5500 cattle from all ages, breeds and sexes were investigated. Prevalence of lumpy skin antibodies was screened by enzyme-linked immunosorbent assay (ELISA) that revealed high exposure rates; 57% and 51.42% in Beni-Suef and Al Fayium governorates respectively Virus isolation was conducted on chorioallantoic membrane (CAM) of specific pathogen free embryonated chicken egg (SPF-ECE) and MDBK cell culture. The virus identity was confirmed by passive haemagglutination and polymerase chain reaction (PCR) on the infected CAM and MDBK cell culture. Experimental infection of rabbits was successful, demonstrating their possible roles in the epidemiological process of the disease.

Experimental Infection of Rabbits with Rabbit and Genotypes 1 and 4 Hepatitis E Viruses

BackgroundA recent study provided evidence that farmed rabbits in China harbor a novel hepatitis E virus (HEV) genotype. Although the rabbit HEV isolate had 77–79% nucleotide identity to the mammalian HEV genotypes 1 to 4, their genomic organization is very similar. Since rabbits are used widely experimentally, including as models of infection, we investigated whether they constitute an appropriate animal model for human HEV infection.MethodsForty-two SPF rabbits were divided randomly into eleven groups and inoculated with six different isolates of rabbit HEV, two different doses of a second-passage rabbit HEV, and with genotype 1 and 4 HEV. Sera and feces were collected weekly after inoculation. HEV antigen, RNA, antibody and alanine aminotransferase in sera and HEV RNA in feces were detected. The liver samples were collected during necropsy subject to histopathological examination.FindingsRabbits inoculated with rabbit HEV became infected with HEV, with viremia, fecal virus shedding and high serum levels of viral antigens, and developed hepatitis, with elevation of the liver enzyme, ALT. The severity of disease corresponded to the infectious dose (genome equivalents), with the most severe hepatic disease caused by strain GDC54-18. However, only two of nine rabbits infected with HEV genotype 4, and none infected with genotype 1, developed hepatitis although six of nine rabbits inoculated with the genotype 1 HEV and in all rabbits inoculated with the genotype 4 HEV seroconverted to be positive for anti-HEV IgG antibody by 14 weeks post-inoculation.ConclusionsThese data indicate that rabbits are an appropriate model for rabbit HEV infection but are not likely to be useful for the study of human HEV. The rabbit HEV infection of rabbits may provide an appropriate parallel animal model to study HEV pathogenesis.

Isolation of Trichophyton mentogrophytes var mentogrophytes from naturally infected laboratory albino rats: experimental infection and treatment in rabbits

The present study demonstrated for the first time the occurrence of dermatophytosis in naturally infected rats and fromasymptomatic and from breeding boxes of white rats kept in animal housing of college of Veterinary Medicine, University ofDohuk, Iraq. The prevalence rate of infection was (28%), clinically infected rats characterized by appearance of scaly ovoidtype lesions with crusty edge and patch of hair loss mostly seen on the back, neck and face of the infected rats, itching wasreported in some rats. Only one species of the trichophyton, T. mentogrophytes var mentogrophytes was isolated with growthrate (85.71%) of samples collected from clinically infected rats, and (28.57%) from asymptomatic and from breeding cages,the growth was observed within the 21 days at 25ºC on Sabouraud's Dextrose Agar. Lacto phenol cotton blue staining slides ofT. mentogrophytes var mentogrophytes revealed both microconidia and macroconidia. Microconidia found in numerousnumbers often in dense cluster which were hyaline, smooth walled and predominantly spherical to sub spherical in shape,varying numbers of chlamydoconidia. Spiral hyphae and smooth, thin walled clavate shaped multicelled macroconidia werealso present. The study also dealt with experimental infection in rabbits with T. mentogrophytes var mentogrophytes andtreated by two drugs, natural herbal preparation of acidic pomegranate (Punica granatum) fruit and synthetic nystatineointment. The complete recovery of lesions was recorded after 14 days and 21 days of topical application of a pomegranateand nystatine ointment for 5 successive days respectively.

Experimental infection of rabbits with a recombinant bovine herpesvirus type 5 (BoHV-5) gI, gE and US9-negative

Bovine herpesvirus type 5 (BoHV-5) is a major cause of viral meningoencephalitis in cattle. The expression of different viral proteins has been associated with BoHV-5 neuropathogenesis. Among these, gI, gE and US9 have been considered essential for the production of neurological disease in infected animals. To evaluate the role of gI, gE and US9 in neurovirulence, a recombinant from which the respective genes were deleted (BoHV-5 gI-/gE-/US9-) was constructed and inoculated in rabbits of two age groups (four and eight weeks-old). When the recombinant virus was inoculated through the paranasal sinuses of four weeks-old rabbits, neurological disease was observed and death was the outcome in 4 out of 13 (30.7 %) animals, whereas clinical signs and death were observed in 11/13 (84.6%) of rabbits infected with the parental virus. In eight weeks-old rabbits, the BoHV-5 gI-/gE-/US9- did not induce clinically apparent disease and could not be reactivated after dexamethasone administration, whereas wild type BoHV-5 caused disease in 55.5% of the animals and was reactivated. These findings reveal that the simultaneous deletion of gI, gE and US9 genes did reduce but did not completely abolish the neurovirulence of BoHV-5 in rabbits, indicating that other viral genes may also play a role in the induction of neurological disease.

Quinolones: action and resistance updated.

The quinolones trap DNA gyrase and DNA topoisomerase IV on DNA as complexes in which the DNA is broken but constrained by protein. Early studies suggested that drug binding occurs largely along helix-4 of the GyrA (gyrase) and ParC (topoisomerase IV) proteins. However, recent X-ray crystallography shows drug intercalating between the -1 and +1 nucleotides of cut DNA, with only one end of the drug extending to helix-4. These two models may reflect distinct structural steps in complex formation. A consequence of drug-enzyme-DNA complex formation is reversible inhibition of DNA replication; cell death arises from subsequent events in which bacterial chromosomes are fragmented through two poorly understood pathways. In one pathway, chromosome fragmentation stimulates excessive accumulation of highly toxic reactive oxygen species that are responsible for cell death. Quinolone resistance arises stepwise through selective amplification of mutants when drug concentrations are above the MIC and below the MPC, as observed with static agar plate assays, dynamic in vitro systems, and experimental infection of rabbits. The gap between MIC and MPC can be narrowed by compound design that should restrict the emergence of resistance. Resistance is likely to become increasingly important, since three types of plasmid-borne resistance have been reported.

Immunobiological characterization of Graphidium strigosum experimental infection in rabbits (Oryctolagus cuniculus)

An experimental infection of rabbits with a wild isolate of the gastric nematode Graphidium strigosum was carried out. Animals (3.5 months age) were infected with 1,000 L3 administered by bucoesophagic catheter (five rabbits) or kept as uninfected control group (five animals). The infection was maintained for 3 months. Along the experimental period, some parasitological, hematological and immunological parameters were determined. Prepatent period of the infection ranged from 30 to 38 days and, at necropsy, average adult helminth counts were 430.75 +/- 126.12. No significant variations were found in packed cell volume, leukocyte, and eosinophil counts along the experimental period. Infection elicited a clear serum-specific IgG response, estimated by ELISA, during patency. Pooled sera from the patent period of the infection recognized some soluble antigens, particularly, a 67-kDa protein. Experimentally infected animals did not show cross recognition between G. strigosum, Haemonchus contortus, and Teladorsagia circumcincta. However, Western blot analysis with hyperimmune sera against H. contortus raised in rabbits and lambs showed cross reactivity between this helminth species and G. strigosum.

Contribution of Panton-Valentine Leukocidin in Community-Associated Methicillin-Resistant Staphylococcus aureus Pathogenesis

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains typically carry genes encoding Panton-Valentine leukocidin (PVL). We used wild-type parental and isogenic PVL-deletion (Δpvl) strains of USA300 (LAC and SF8300) and USA400 (MW2) to test whether PVL alters global gene regulatory networks and contributes to pathogenesis of bacteremia, a hallmark feature of invasive staphylococcal disease. Microarray and proteomic analyses revealed that PVL does not alter gene or protein expression, thereby demonstrating that any contribution of PVL to CA-MRSA pathogenesis is not mediated through interference of global gene regulatory networks. Inasmuch as a direct role for PVL in CA-MRSA pathogenesis remains to be determined, we developed a rabbit bacteremia model of CA-MRSA infection to evaluate the effects of PVL. Following experimental infection of rabbits, an animal species whose granulocytes are more sensitive to the effects of PVL compared with the mouse, we found a contribution of PVL to pathogenesis over the time course of bacteremia. At 24 and 48 hours post infection, PVL appears to play a modest, but measurable role in pathogenesis during the early stages of bacteremic seeding of the kidney, the target organ from which bacteria were not cleared. However, the early survival advantage of this USA300 strain conferred by PVL was lost by 72 hours post infection. These data are consistent with the clinical presentation of rapid-onset, fulminant infection that has been associated with PVL-positive CA-MRSA strains. Taken together, our data indicate a modest and transient positive effect of PVL in the acute phase of bacteremia, thereby providing evidence that PVL contributes to CA-MRSA pathogenesis.