Publications by authors named "Daniel W Martin"

12 Publications

  • Page 1 of 1

Uncovering the Hidden Credentials of Virulence.

Microbiol Mol Biol Rev 2021 02 10;85(1). Epub 2021 Feb 10.

Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.

Bacteria in the genus are important human and veterinary pathogens. The abortion and infertility they cause in food animals produce economic hardships in areas where the disease has not been controlled, and human brucellosis is one of the world's most common zoonoses. strains have also been isolated from wildlife, but we know much less about the pathobiology and epidemiology of these infections than we do about brucellosis in domestic animals. The brucellae maintain predominantly an intracellular lifestyle in their mammalian hosts, and their ability to subvert the host immune response and survive and replicate in macrophages and placental trophoblasts underlies their success as pathogens. We are just beginning to understand how these bacteria evolved from a progenitor alphaproteobacterium with an environmental niche and diverged to become highly host-adapted and host-specific pathogens. Two important virulence determinants played critical roles in this evolution: (i) a type IV secretion system that secretes effector molecules into the host cell cytoplasm that direct the intracellular trafficking of the brucellae and modulate host immune responses and (ii) a lipopolysaccharide moiety which poorly stimulates host inflammatory responses. This review highlights what we presently know about how these and other virulence determinants contribute to pathogenesis. Gaining a better understanding of how the brucellae produce disease will provide us with information that can be used to design better strategies for preventing brucellosis in animals and for preventing and treating this disease in humans.
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http://dx.doi.org/10.1128/MMBR.00021-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8549849PMC
February 2021

Multidisciplinary Community-Based Investigation of a COVID-19 Outbreak Among Marshallese and Hispanic/Latino Communities - Benton and Washington Counties, Arkansas, March-June 2020.

MMWR Morb Mortal Wkly Rep 2020 Dec 4;69(48):1807-1811. Epub 2020 Dec 4.

By June 2020, Marshallese and Hispanic or Latino (Hispanic) persons in Benton and Washington counties of Arkansas had received a disproportionately high number of diagnoses of coronavirus disease 2019 (COVID-19). Despite representing approximately 19% of these counties' populations (1), Marshallese and Hispanic persons accounted for 64% of COVID-19 cases and 57% of COVID-19-associated deaths. Analyses of surveillance data, focus group discussions, and key-informant interviews were conducted to identify challenges and propose strategies for interrupting transmission of SARS-CoV-2, the virus that causes COVID-19. Challenges included limited native-language health messaging, high household occupancy, high employment rate in the poultry processing industry, mistrust of the medical system, and changing COVID-19 guidance. Reducing the COVID-19 incidence among communities that suffer disproportionately from COVID-19 requires strengthening the coordination of public health, health care, and community stakeholders to provide culturally and linguistically tailored public health education, community-based prevention activities, case management, care navigation, and service linkage.
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http://dx.doi.org/10.15585/mmwr.mm6948a2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714036PMC
December 2020

Investigating the roles of the conserved Cu-binding residues on Brucella FtrA in producing conformational stability and functionality.

J Inorg Biochem 2020 09 23;210:111162. Epub 2020 Jun 23.

Department of Chemistry, Amity Institute of Applied Sciences, Amity University Kolkata, WB, 700135, India.

Brucella is a zoonotic pathogen requiring iron for its survival and acquires this metal through the expression of several high-affinity uptake systems. Of these, the newly discovered ferrous iron transporter, FtrABCD, is proposed to take part in ferrous iron uptake. Sequence homology shows that, FtrA, the proposed periplasmic ferrous-binding component, is a P19-type protein (a periplasmic protein from C. jejuni which shows Cu dependent iron affinity). Previous structural and biochemical studies on other P19 systems have established a Cu dependent Mn affinity as well as formation of homodimers for these systems. The Cu coordinating amino acids from these proteins are conserved in Brucella FtrA, hinting towards similar properties. However, there has been no experimental evidence, till date, establishing metal affinities and the possibility of dimer formation by Brucella FtrA. Using wild-type FtrA and Cu-binding mutants (H65A, E67A, H118A, and H151A) we investigated the metal affinities, folding stabilities, dimer forming abilities, and the molecular basis of the Cu dependence for this P19-type protein employing homology modeling, analytical gel filtration, calorimetric, and spectroscopic methods. The data reported here confirm a Cu-dependent, low-μM Mn (Fe mimic) affinity for the wild-type FtrA. In addition, our data clearly show the loss of Mn affinity, and the formation of less stable protein conformations as a result of mutating these conserved Cu-binding residues, indicating the important roles these residues play in producing a native and functional fold of Brucella FtrA.
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http://dx.doi.org/10.1016/j.jinorgbio.2020.111162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484176PMC
September 2020

Implementing Nationwide Facility-based Electronic Disease Surveillance in Sierra Leone: Lessons Learned.

Health Secur 2020 Jan;18(S1):S72-S80

Daniel W. Martin, MSPH, is an Epidemiologist, and Michelle L. Sloan, MA, is a Health Scientist; both in the Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA. Brigette L. Gleason, MD, is Surveillance and Program Lead; Ansumana Kamara is a Public Health Specialist; and Tushar Singh, MD, PhD, is Country Director; all in the CDC Sierra Leone Country Office, Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Freetown, Sierra Leone. Les de Wit, MIntDev, is Information Systems Manager, Global Health Informatics, and Nelson Clemens, MBA, is eIDSR Project Coordinator, Disease Surveillance Systems; both with eHealth Africa, Freetown, Sierra Leone. Mohamed Alex Vandi, MD, is Director of Health Security and Emergencies, Ministry of Health and Sanitation, Freetown, Sierra Leone. David K. Kargbo is with the Ministry of Health and Sanitation, Freetown, Sierra Leone. Charles Njuguna, PhD, is Health Security and Emergency Cluster Lead, and Stephen Sesay is Data Manager/GIS Analyst; both with the World Health Organization, Freetown, Sierra Leone. The views expressed are the authors' own and do not necessarily represent the views of the Centers for Disease Control and Prevention, the US government, or the World Health Organization.

The Global Health Security Agenda aims to improve countries' ability to prevent, detect, and respond to infectious disease threats by building or strengthening core capacities required by the International Health Regulations (2005). One of those capacities is the development of surveillance systems to rapidly detect and respond to occurrences of diseases with epidemic potential. Since 2015, the US Centers for Disease Control and Prevention (CDC) has worked with partners in Sierra Leone to assist the Ministry of Health and Sanitation in developing an Integrated Disease Surveillance and Response (IDSR) system. Beginning in 2016, CDC, in collaboration with the World Health Organization and eHealth Africa, has supported the ministry in the development of Android device mobile data entry at the health facility for electronic IDSR (eIDSR), also known as health facility-based eIDSR. Health facility-based eIDSR was introduced via a pilot program in 1 district, and national rollout began in 2018. With more than 1,100 health facilities now reporting, the Sierra Leone eIDSR system is substantially larger than most mobile-device health (mHealth) projects found in the literature. Several technical innovations contributed to the success of health facility-based eIDSR in Sierra Leone. Among them were data compression and dual-mode (internet and text) message transmission to mitigate connectivity issues, user interface design tailored to local needs, and a continuous-feedback process to iteratively detect user or system issues and remediate challenges identified. The resultant system achieved high user acceptance and demonstrated the feasibility of an mHealth-based surveillance system implemented on a national scale.
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http://dx.doi.org/10.1089/hs.2019.0081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465552PMC
January 2020

The Cation Diffusion Facilitator Family Protein EmfA Confers Resistance to Manganese Toxicity in Brucella abortus 2308 and Is an Essential Virulence Determinant in Mice.

J Bacteriol 2019 12 6;202(1). Epub 2019 Dec 6.

Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA

The gene designated in the 2308 genome encodes an ortholog of the cation diffusion facilitator family protein EmfA which has been linked to resistance to Mn toxicity in A null mutant derived from strain 2308 displays increased sensitivity to elevated levels of Mn in the growth medium compared to that of the parent strain but wild-type resistance to Fe, Mg, Zn, Cu, Co, and Ni. Inductively coupled plasma mass spectroscopy also indicates that the mutant retains significantly higher levels of cellular Mn after exposure to this metal than the parent strain, which is consistent with the proposed role of EmfA as a Mn exporter. Phenotypic analysis of mutants indicates that EmfA plays a much more important role in maintaining Mn homeostasis and preventing the toxicity of this metal in than does the Mn-responsive transcriptional regulator Mur. EmfA is also an essential virulence determinant for 2308 in C57BL/6 and C57BL/6 mice, which suggests that avoiding Mn toxicity plays a critical role in pathogenesis. Mn nutrition is essential for the basic physiology and virulence of strains. The results of the study presented here demonstrate that the cation diffusion facilitator (CDF)-type metal exporter EmfA plays critical roles in maintaining Mn homeostasis and preventing Mn toxicity in and is an essential virulence determinant for these bacteria. EmfA and other cellular components involved in Mn homeostasis represent attractive targets for the development of improved vaccines and chemotherapeutic strategies for preventing and treating brucellosis in humans and animals.
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http://dx.doi.org/10.1128/JB.00357-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932235PMC
December 2019

The Manganese-Dependent Pyruvate Kinase PykM Is Required for Wild-Type Glucose Utilization by Brucella abortus 2308 and Its Virulence in C57BL/6 Mice.

J Bacteriol 2018 12 26;200(24). Epub 2018 Nov 26.

Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA

Pyruvate kinase plays a central role in glucose catabolism in bacteria, and efficient utilization of this hexose has been linked to the virulence of strains in mice. The brucellae produce a single pyruvate kinase which is an ortholog of the manganese (Mn)-dependent pyruvate kinase PykM. A biochemical analysis of the pyruvate kinase and phenotypic analysis of a mutant defective in high-affinity Mn import indicate that this enzyme is an authentic PykM ortholog which functions as a Mn-dependent enzyme The loss of PykM has a negative impact on the capacity of the parental 2308 strain to utilize glucose, fructose, and galactose but not on its ability to utilize ribose, xylose, arabinose, or erythritol, and a mutant displays significant attenuation in C57BL/6 mice. Although the enzyme pyruvate phosphate dikinase (PpdK) can substitute for the loss of pyruvate kinase in some bacteria and is also an important virulence determinant in , a phenotypic analysis of 2308 and isogenic , , and mutants indicates that PykM and PpdK make distinctly different contributions to carbon metabolism and virulence in these bacteria. Mn plays a critical role in the physiology and virulence of strains, and the results presented here suggest that one of the important roles that the high-affinity Mn importer MntH plays in the pathogenesis of these strains is supporting the function of the Mn-dependent kinase PykM. A better understanding of how the brucellae adapt their physiology and metabolism to sustain their intracellular persistence in host macrophages will provide knowledge that can be used to design improved strategies for preventing and treating brucellosis, a disease that has a significant impact on both the veterinary and public health communities worldwide.
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http://dx.doi.org/10.1128/JB.00471-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256021PMC
December 2018

Notes from The Field: Ebola Virus Disease Cluster - Northern Sierra Leone, January 2016.

MMWR Morb Mortal Wkly Rep 2016 Jul 8;65(26):681-2. Epub 2016 Jul 8.

On January 14, 2016, the Sierra Leone Ministry of Health and Sanitation was notified that a buccal swab collected on January 12 from a deceased female aged 22 years (patient A) in Tonkolili District had tested positive for Ebola virus by reverse transcription-polymerase chain reaction (RT-PCR). The most recent case of Ebola virus disease (Ebola) in Sierra Leone had been reported 4 months earlier on September 13, 2015 (1), and the World Health Organization had declared the end of Ebola virus transmission in Sierra Leone on November 7, 2015 (2). The Government of Sierra Leone launched a response to prevent further transmission of Ebola virus by identifying contacts of the decedent and monitoring them for Ebola signs and symptoms, ensuring timely treatment for anyone with Ebola, and conducting an epidemiologic investigation to identify the source of infection.
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http://dx.doi.org/10.15585/mmwr.mm6526a4DOI Listing
July 2016

Immunization information systems: a decade of progress in law and policy.

J Public Health Manag Pract 2015 May-Jun;21(3):296-303

Immunization Information Systems Support Branch, Immunization Services Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia (Mr Martin); Public Health Informatics Institute, Decatur, Georgia (Ms Lowery); Public Health Informatics Institute, Decatur, Georgia (Mr Brand); National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia (Ms Gold); and Office of the Associate Director for Science, Centers for Disease Control and Prevention, Atlanta, Georgia (Ms Horlick).

This article reports on a study of laws, regulations, and policies governing Immunization Information Systems (IIS, also known as "immunization registries") in states and selected urban areas of the United States. The study included a search of relevant statutes, administrative codes and published attorney general opinions/findings, an online questionnaire completed by immunization program managers and/or their staff, and follow-up telephone interviews.The legal/regulatory framework for IIS has changed considerably since 2000, largely in ways that improve IIS' ability to perform their public health functions while continuing to maintain strict confidentiality and privacy controls. Nevertheless, the exchange of immunization data and other health information between care providers and public health and between entities in different jurisdictions remains difficult due in part to ongoing regulatory diversity.To continue to be leaders in health information exchange and facilitate immunization of children and adults, IIS will need to address the challenges presented by the interplay of federal and state legislation, regulations, and policies and continue to move toward standardized data collection and sharing necessary for interoperable systems.
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http://dx.doi.org/10.1097/PHH.0000000000000040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671281PMC
December 2016

Characterization of the organic hydroperoxide resistance system of Brucella abortus 2308.

J Bacteriol 2012 Sep 20;194(18):5065-72. Epub 2012 Jul 20.

Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina, USA.

The organic hydroperoxide resistance protein Ohr has been identified in numerous bacteria where it functions in the detoxification of organic hydroperoxides, and expression of ohr is often regulated by a MarR-type regulator called OhrR. The genes annotated as BAB2_0350 and BAB2_0351 in the Brucella abortus 2308 genome sequence are predicted to encode OhrR and Ohr orthologs, respectively. Using isogenic ohr and ohrR mutants and lacZ promoter fusions, it was determined that Ohr contributes to resistance to organic hydroperoxide, but not hydrogen peroxide, in B. abortus 2308 and that OhrR represses the transcription of both ohr and ohrR in this strain. Moreover, electrophoretic mobility shift assays and DNase I footprinting revealed that OhrR binds directly to a specific region in the intergenic region between ohr and ohrR that shares extensive nucleotide sequence similarity with so-called "OhrR boxes" described in other bacteria. While Ohr plays a prominent role in protecting B. abortus 2308 from organic hydroperoxide stress in in vitro assays, this protein is not required for the wild-type virulence of this strain in cultured murine macrophages or experimentally infected mice.
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http://dx.doi.org/10.1128/JB.00873-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430311PMC
September 2012

SodA is a major metabolic antioxidant in Brucella abortus 2308 that plays a significant, but limited, role in the virulence of this strain in the mouse model.

Microbiology (Reading) 2012 Jul 3;158(Pt 7):1767-1774. Epub 2012 May 3.

Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA.

The gene designated BAB1_0591 in the Brucella abortus 2308 genome sequence encodes the manganese-cofactored superoxide dismutase SodA. An isogenic sodA mutant derived from B. abortus 2308, designated JB12, displays a small colony phenotype, increased sensitivity in vitro to endogenous superoxide generators, hydrogen peroxide and exposure to acidic pH, and a lag in growth when cultured in rich and minimal media that can be rescued by the addition of all 20 amino acids to the growth medium. B. abortus JB12 exhibits significant attenuation in both cultured murine macrophages and experimentally infected mice, but this attenuation is limited to the early stages of infection. Addition of the NADPH oxidase inhibitor apocynin to infected macrophages does not alleviate the attenuation exhibited by JB12, suggesting that the basis for the attenuation of the B. abortus sodA mutant is not an increased sensitivity to exogenous superoxide generated through the oxidative burst of host phagocytes. It is possible, however, that the increased sensitivity of the B. abortus sodA mutant to acid makes it less resistant than the parental strain to killing by the low pH encountered during the early stages of the development of the brucella-containing vacuoles in macrophages. These experimental findings support the proposed role for SodA as a major cytoplasmic antioxidant in brucella. Although this enzyme provides a clear benefit to B. abortus 2308 during the early stages of infection in macrophages and mice, SodA appears to be dispensable once the brucellae have established an infection.
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http://dx.doi.org/10.1099/mic.0.059584-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3542146PMC
July 2012

Survival of the fittest: how Brucella strains adapt to their intracellular niche in the host.

Med Microbiol Immunol 2009 Nov 22;198(4):221-38. Epub 2009 Sep 22.

Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.

Brucella strains produce abortion and infertility in their natural hosts and a zoonotic disease in humans known as undulant fever. These bacteria do not produce classical virulence factors, and their capacity to successfully survive and replicate within a variety of host cells underlies their pathogenicity. Extensive replication of the brucellae in placental trophoblasts is associated with reproductive tract pathology in natural hosts, and prolonged persistence in macrophages leads to the chronic infections that are a hallmark of brucellosis in both natural hosts and humans. This review describes how Brucella strains have efficiently adapted to their intracellular lifestyle in the host.
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http://dx.doi.org/10.1007/s00430-009-0123-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814008PMC
November 2009

The manganese transporter MntH is a critical virulence determinant for Brucella abortus 2308 in experimentally infected mice.

Infect Immun 2009 Aug 1;77(8):3466-74. Epub 2009 Jun 1.

Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27834, USA.

The gene designated BAB1_1460 in the Brucella abortus 2308 genome sequence is predicted to encode the manganese transporter MntH. Phenotypic analysis of an isogenic mntH mutant indicates that MntH is the sole high-affinity manganese transporter in this bacterium but that MntH does not play a detectable role in the transport of Fe(2+), Zn(2+), Co(2+), or Ni(2+). Consistent with the apparent selectivity of the corresponding gene product, the expression of the mntH gene in B. abortus 2308 is repressed by Mn(2+), but not Fe(2+), and this Mn-responsive expression is mediated by a Mur-like repressor. The B. abortus mntH mutant MWV15 exhibits increased susceptibility to oxidative killing in vitro compared to strain 2308, and a comparative analysis of the superoxide dismutase activities present in these two strains indicates that the parental strain requires MntH in order to make wild-type levels of its manganese superoxide dismutase SodA. The B. abortus mntH mutant also exhibits extreme attenuation in both cultured murine macrophages and experimentally infected C57BL/6 mice. These experimental findings indicate that Mn(2+) transport mediated by MntH plays an important role in the physiology of B. abortus 2308, particularly during its intracellular survival and replication in the host.
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http://dx.doi.org/10.1128/IAI.00444-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715675PMC
August 2009
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