Borrelia burgdorferi, the agent of Lyme borreliosis, can elude hosts' innate and adaptive immunity as part of the course of infection. The ability of B. burgdorferi to invade or be internalized by ...host cells in vitro has been proposed as a mechanism for the pathogen to evade immune responses or antimicrobials. We have previously shown that B. burgdorferi can be internalized by human neuroglial cells. In this study we demonstrate that these cells take up B. burgdorferi via coiling phagocytosis mediated by the formin, Daam1, a process similarly described for human macrophages. Following coincubation with glial cells, B. burgdorferi was enwrapped by Daam1-enriched coiling pseudopods. Coiling of B. burgdorferi was significantly reduced when neuroglial cells were pretreated with anti-Daam1 antibody indicating the requirement for Daam1 for borrelial phagocytosis. Confocal microscopy showed Daam1 colocalizing to the B. burgdorferi surface suggesting interaction with borrelial membrane protein(s). Using the yeast 2-hybrid system for identifying protein-protein binding, we found that the B. burgdorferi surface lipoprotein, BBA66, bound the FH2 subunit domain of Daam1. Recombinant proteins were used to validate binding by ELISA, pull-down, and co-immunoprecipitation. Evidence for native Daam1 and BBA66 interaction was suggested by colocalization of the proteins in the course of borrelial capture by the Daam1-enriched pseudopodia. Additionally, we found a striking reduction in coiling for a BBA66-deficient mutant strain compared to BBA66-expressing strains. These results show that coiling phagocytosis is a mechanism for borrelial internalization by neuroglial cells mediated by Daam1.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Monkeypox virus (MPXV) is a member of the genus Orthopoxvirus, endemic in Central and West Africa. This viral zoonosis was introduced into the United States in 2003 via African rodents imported for ...the pet trade and caused 37 human cases, all linked to exposure to MPXV-infected black-tailed prairie dogs (Cynomys ludovicianus). Prairie dogs have since become a useful model of MPXV disease, utilized for testing of potential medical countermeasures. In this study, we used recombinant MPXV containing the firefly luciferase gene (luc) and in vivo imaging technology to characterize MPXV pathogenesis in the black-tailed prairie dog in real time. West African (WA) MPXV could be visualized using in vivo imaging in the nose, lymph nodes, intestines, heart, lung, kidneys, and liver as early as day 6 post infection (p.i.). By day 9 p.i., lesions became visible on the skin and in some cases in the spleen. After day 9 p.i., luminescent signal representing MPXV replication either increased, indicating a progression to what would be a fatal infection, or decreased as infection was resolved. Use of recombinant luc+ MPXV allowed for a greater understanding of how MPXV disseminates throughout the body in prairie dogs during the course of infection. This technology will be used to reduce the number of animals required in future pathogenesis studies as well as aid in determining the effectiveness of potential medical countermeasures.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Maintaining cold chain while transporting medical supplies and samples is difficult in remote settings. Failure to maintain temperature requirements can lead to degraded sample quality and ...inaccuracies in sample analysis. We performed a systematic analysis on different types of transport coolers (polystyrene foam, injection-molded, and rotational molded) and transport coolants (ice, cold packs, frozen water bottles) frequently in use in many countries. Polystyrene foam coolers stayed below our temperature threshold (6°C) longer than almost all other types of coolers, but were not durable. Injection-molded coolers were durable, but warmed to 6°C the quickest. Rotational molded coolers were able to keep temperatures below our threshold for 24 hours longer than injection molded coolers and were highly durable. Coolant systems were evaluated in terms of cost and their ability to maintain cold temperatures. Long lasting commercial cold packs were found to be less cost effective and were below freezing for the majority of the testing period. Frozen plastic water bottles were found to be a reusable and economical choice for coolant and were only below freezing briefly. Finally, we modeled the coolers performance at maintaining internal temperatures below 6°C and built a highly accurate linear model to predict how long a cooler will remain below 6°C. We believe this data may be useful in the planning and design of specimen transportation systems in the field, particularly in remote or resource limited settings.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Burkholderia thailandensis, an opportunistic pathogen found in the environment, is a bacterium closely related to B. pseudomallei, the cause of melioidosis. Human B. thailandensis infections are ...uncommon. We isolated B. thailandensis from water in Texas and Puerto Rico and soil in Mississippi in the United States, demonstrating a potential public health risk.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Melioidosis, caused by the bacterium
Burkholderia pseudomallei,
is an uncommon infection that is typically associated with exposure to soil and water in tropical and subtropical environments. It is ...rarely diagnosed in the continental United States. Patients with melioidosis in the United States commonly report travel to regions where melioidosis is endemic. We report a cluster of four non–travel-associated cases of melioidosis in Georgia, Kansas, Minnesota, and Texas. These cases were caused by the same strain of
B. pseudomallei
that was linked to an aromatherapy spray product imported from a melioidosis-endemic area.
Four cases of non–travel-associated melioidosis (caused by
Burkholderia pseudomallei
) that were identified across the United States were associated with the use of a contaminated aromatherapy room spray.
Melioidosis, caused by
Burkholderia pseudomallei
, is a rare but potentially fatal bacterial disease endemic to tropical and subtropical regions worldwide. It is typically acquired through contact ...with contaminated soil or fresh water. Before this investigation,
B. pseudomallei
was not known to have been isolated from the environment in the continental United States. Here, we report on three patients living in the same Mississippi Gulf Coast county who presented with melioidosis within a 3-year period. They were infected by the same Western Hemisphere
B. pseudomallei
strain that was discovered in three environmental samples collected from the property of one of the patients. These findings indicate local acquisition of melioidosis from the environment in the Mississippi Gulf Coast region.
This report describes three rare cases of melioidosis (caused by
Burkholderia pseudomallei
) that were locally acquired in Mississippi.
Periprosthetic fractures (PPFXs) are becoming increasingly common following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Patients sustaining PPFXs face considerable perioperative ...morbidity, with relatively increased rates of surgical site infection. We sought to evaluate the efficacy of closed-incision negative-pressure wound therapy (ciNPT) in decreasing perioperative wound complications following lower extremity periprosthetic fracture surgery.
We performed a retrospective review of 69 consecutive patients who underwent surgery to address lower extremity periprosthetic fractures around hip or knee implants performed over a 6.5-year period. The population was divided into two groups based on the surgical dressing used at the conclusion of the procedure: (1) a sterile, antimicrobial hydrofiber dressing, or (2) ciNPT. There were no baseline demographic differences between the two groups. Rates of wound complications, surgical site infection, and reoperation related to the surgical site were compared between groups. Continuous variables were analyzed using a student’s t-test, and categorical variables using either chi-square or fisher’s exact test.
Patients treated with ciNPT developed fewer wound complications (4% vs. 35%; p=0.002), fewer deep infections (0% vs. 25%; p=0.004), and underwent fewer reoperations related to the surgical site (4% vs. 25%; p=0.021) compared to patients treated with standard of care.
Our findings suggest that ciNPT may reduce wound complications, SSIs, and reoperations in patients undergoing lower extremity periprosthetic fracture surgery. This is the first study to investigate ciNPT as a treatment for periprosthetic fracture surgery, and has the potential to change the postoperative management of these patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Borrelia burgdorferi synthesizes an HtrA protease (BbHtrA) which is a surface-exposed, conserved protein within Lyme disease spirochetes with activity toward CheX and BmpD of Borrelia spp, as well as ...aggrecan, fibronectin and proteoglycans found in skin, joints and neural tissues of vertebrates. An antibody response against BbHtrA is observed in Lyme disease patients and in experimentally infected laboratory mice and rabbits. Given the surface location of BbHtrA on B. burgdorferi and its ability to elicit an antibody response in infected hosts, we explored recombinant BbHtrA as a potential vaccine candidate in a mouse model of tick-transmitted Lyme disease. We immunized mice with two forms of BbHtrA: the proteolytically active native form and BbHtrA ablated of activity by a serine to alanine mutation at amino acid 226 (BbHtrA(S226A)). Although inoculation with either BbHtrA or BbHtrA(S226A) produced high-titer antibody responses in C3H/HeJ mice, neither antigen was successful in protecting mice from B. burgdorferi challenge. These results indicate that the search for novel vaccine candidates against Lyme borreliosis remains a challenge.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aseptic loosening is a considerable complication that affects the longevity of total knee arthroplasty (TKA) implants. Surgeon technique may help minimize aseptic loosening after TKA. Meticulous ...cementation of the prosthesis and the bone surface during various stages of cement polymerization will maximize cement adherence to the prosthesis and the bone, respectively. Pressurization of the cement in the canal and at the cut surface to achieve at least 2 mm of cement depth penetration has been reported to increase TKA implant longevity.
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