Biology subjects

Hasenkampf, N. R.

Publications and source records attributed to Hasenkampf, N. R..

3 recordsLinked to original sources

bioRxiv2023

Superior Efficacy of Combination Antibiotic Therapy versus Monotherapy in a Mouse Model of Lyme Disease

Lyme disease (LD) results from the most prevalent tick-borne infection in North America, with over 476,000 estimated cases annually. The disease is caused by Borrelia burgdorferi (Bb) which transmits through the bite of Ixodid ticks. Most cases treated soon after infection are resolved by a short course of oral antibiotics. However, 10-20% of patients experience chronic symptoms because of delayed or incomplete treatment, a condition called Post-Treatment Lyme Disease (PTLD). Some Bb persists in PTLD patients after the initial course of antibiotics and an effective treatment to eradicate the persistent Bb is needed. Other organisms that cause persistent infections, such as M. tuberculosis, are cleared using a combination of therapies rather than monotherapy. A group of Food and Drug Administration (FDA)-approved drugs efficacious against Bb were used in monotherapy or in combination in mice infected with Bb. Different methods of detection were used to assess the efficacy of the treatments in the infected mice including culture, xenodiagnosis, and molecular techniques. None of the monotherapies eradicated persistent Bb. However, 4 dual combinations (doxycycline + ceftriaxone, dapsone + rifampicin, dapsone + clofazimine, doxycycline + cefotaxime) and 3 triple combinations (doxycycline + ceftriaxone+ carbomycin, doxycycline + cefotaxime+ loratadine, dapsone+ rifampicin+ clofazimine) eradicated persistent Bb infections. These results suggest that combination therapy should be investigated in preclinical studies for treating human Lyme disease.

microbiology↗

bioRxiv2020

Visualizing Borrelia burgdorferi infection using a small molecule imaging probe.

In vivo diagnostic imaging of bacterial infections is currently reliant on targeting their metabolic pathways, an ineffective method to identify microbial species with low metabolic activity. Here we establish HS-198 as a small molecule-fluorescent conjugate that selectively targets the highly conserved bacterial protein, HtpG (High temperature protein G), within B. burgdorferi, the bacteria responsible for Lyme Disease. We describe the use of HS-198 to target morphologic forms of B. burgdorferi in both the logarithmic growth phase and the metabolically dormant stationary phase. Furthermore, in a murine infection model, systemically injected HS-198 identified B. burgdorferi as revealed by imaging in post necropsy tissue sections. These findings demonstrate how small molecule probes directed at conserved bacterial protein targets can function to identify the microbe using non-invasive imaging and potentially as scaffolds to deliver antimicrobial agents to the pathogen.

microbiology↗

bioRxiv2018

Immunological responses to the relapsing fever spirochete Borrelia turicatae in infected Rhesus macaques: implications for pathogenesis and diagnosis.

The global public health impact of relapsing fever (RF) spirochetosis is significant, as the pathogens exist on five of seven continents. The hallmark sign of infection is episodic fever and the greatest threat is to the unborn. With the goal of better understanding the specificity of B cell responses and the role of immune responses in pathogenicity, we infected Rhesus macaques with Borrelia turicatae (a new world RF spirochete species) by tick bite and monitored the immune responses generated in response to the pathogen. Specifically, we evaluated inflammatory mediator induction by the pathogen, host antibody responses to specific antigens, and peripheral lymphocyte population dynamics. Our results indicate that B. turicatae elicits from peripheral blood cells key inflammatory response mediators (IL-1{beta} and TNF-) which are associated with pre-term abortion. Moreover, a global decline in peripheral B cell populations was observed in all animals at 14 days post-infection. Serological responses were also evaluated to assess the antigenicity of three surface proteins, BipA, BrpA and Bta112. Interestingly, a distinction was observed between antibodies generated in non-human primates (NHPs) and mice. Our results provide support for the nonhuman primate model not only in studies of prenatal pathogenesis, but for diagnostic and vaccine antigen identification and testing.

immunology↗