Restricted Identification of Clinical Pathogens Categorized as Biothreats by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry

Keller, Peter M.; Bruderer, Vera; Müller, Franco B.

doi:10.1128/jcm.03250-15

Cited by 16 publications

(15 citation statements)

References 5 publications

(5 reference statements)

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“…The inability to differentiate high-consequence pathogens from related bacterial species can be a serious issue for clinical diagnostic laboratories and more so in a biothreat perspective 28,50,54 . Incorrect identifications with single MALDI-TOF MS methods have resulted in laboratory exposures with Francisella tularensis 55 and B. pseudomallei 56 .…”

Section: Discussionmentioning

confidence: 99%

Elucidation of protein biomarkers for verification of selected biological warfare agents using tandem mass spectrometry

Rajoria

Sabna

Babele

et al. 2020

Sci Rep

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Some pathogens and toxins have the potential to be used as weapons of mass destruction and instigate population-based fear. Efforts to mitigate biothreat require development of efficient countermeasures which in turn relies on fast and accurate methods to detect the biological agents in a range of complex matrices including environmental and clinical samples. We report here an mass spectrometry (MS) based methodology, employing both targeted and shot-gun approaches for the verification of biological agents from the environmental samples. our shot-gun methodology relied on tandem MS analysis of abundant peptides from the spiked samples, whereas, the targeted method was based on an extensive elucidation of marker proteins and unique peptides resulting in the generation of an inclusion list of masses reflecting relevant peptides for the unambiguous identification of nine bacterial species [listed as priority agents of bioterrorism by centre for Disease control and prevention (cDc)] belonging to phylogenetically diverse genera. the marker peptides were elucidated by extensive literature mining, in silico analysis, and tandem MS (MS/MS) analysis of abundant proteins of the cultivated bacterial species in our laboratory. A combination of shot-gun MS/MS analysis and the targeted search using a panel of unique peptides is likely to provide unambiguous verification of biological agents at subspecies level, even with limited fractionation of crude protein extracts from environmental samples. the comprehensive list of peptides reflected in the inclusion list, makes a valuable resource for the multiplex analysis of select biothreat agents and further development of targeted MS/MS assays.The realization that that some pathogenic microbes and toxins of biological origin can be used as weapons of mass destruction has gained prominence especially in the backdrop of growing concerns for bioterrorism. Biological select agents are derived from biological sources, are capable of causing significant damage to human health and safety, and can be overtly or covertly used for ideological, political, or financial gain 1 . U.S. Department of Health and Human Services (HHS) and the U.S. Department of Agriculture (USDA) have prioritized these select agents 2 and CDC has classified the agents of bioterrorism under the categories A through C 3 . It includes several toxins, bacteria, and viruses that are prioritized based on their high morbidity and mortality, dose of infections, environmental stability, production ease, and lack of an established countermeasure. Our vulnerability to biological warfare agents was realized after the anthrax letter attack of 2001 4 ; the mortality rate of inhalational anthrax is 100% when left untreated. The high-consequence bacterial biowarfare (BW) agents encompass wide phylogenetic lineages including the causative agents of plague (Yersinia pestis), anthrax (Bacillus anthracis), brucellosis (Brucella spp), and tularaemia (Francisella tularensis). Missile warheads, manned or unmanned spray-tanks coupled to the...

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Section: Discussionmentioning

confidence: 99%

Elucidation of protein biomarkers for verification of selected biological warfare agents using tandem mass spectrometry

Rajoria

Sabna

Babele

et al. 2020

Sci Rep

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“…There is also a significant public health and occupational health issue in cases where F. tularensis is cultured in a routine bench in microbiological laboratory from an unsuspecting sample. Every institution has a different approach; in the Czech case, all contacts were offered prophylactic doxycycline without seroconversion testing, while in the Swiss case, only observation for seroconversion was performed (23).…”

Section: Discussionmentioning

confidence: 99%

Francisella tularensis Periprosthetic Joint Infections Diagnosed with Growth in Cultures

et al. 2019

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Tularemia caused by Francisella tularensis is a zoonotic infection of the Northern Hemisphere that mainly affects the skin, lymph nodes, bloodstream, and lungs. Other manifestations of tularemia are very rare, especially those with musculoskeletal involvement. Presenting in 2016, we diagnosed two cases of periprosthetic knee joint infections (PJI) caused by Francisella tularensis in Europe (one in Switzerland and one in the Czech Republic). We found only two other PJI cases in the literature, another knee PJI diagnosed 1999 in Ontario, Canada, and one hip PJI in Illinois, USA, in 2017. Diagnosis was made in all cases by positive microbiological cultures after 3, 4, 7, and 12 days. All were successfully treated, two cases by exchange of the prosthesis, one with debridement and retention, and one with repeated aspiration of the synovial fluid only. Antibiotic treatment was given between 3 weeks and 12 months with either ciprofloxacin-rifampin or with doxycycline alone or doxycycline in combination with gentamicin. Zoonotic infections should be considered in periprosthetic infections in particular in culture-negative PJIs with a positive histology or highly elevated leukocyte levels in synovial aspiration. Here, we recommend prolonging cultivation time up to 14 days, performing specific PCR tests, and/or conducting epidemiologically appropriate serological tests for zoonotic infections, including that for F. tularensis.

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“…Au total, 39 personnes ont été exposées à des ABCSE du GR3 dans six incidents d'exposition liés à l'utilisation de la SM MALDI-TOF. Ces microorganismes correspondent à ceux ayant été impliqués dans d'autres incidents signalés dans la littérature (3,(10)(11)(12)15,19,22).…”

Section: Discussionunclassified

“…Des études ont indiqué que l'identification erronée des microorganismes par SM MALDI-TOF semble être attribuable à l'incomplétude des bases de données de référence utilisées (2,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Deux types de bases de données de référence sont actuellement utilisées au Canada : les bases de données cliniques, contenant les spectres approuvés par Santé Canada, et les bases de données de recherche, qui contiennent un plus vaste ensemble de spectres, mais dont l'application clinique n'a pas été autorisée.…”

Section: Affiliation Introductionunclassified

Erreurs d'identification des agents biologiques à cote de sécurité élevée du groupe de risque 3 par SM MALDI-TOF au Canada : de novembre 2015 à octobre 2017

Pomerleau-Normandin¹,

Heisz²,

Su³

2018

RMTC

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Restricted Identification of Clinical Pathogens Categorized as Biothreats by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry

Cited by 16 publications

References 5 publications

Elucidation of protein biomarkers for verification of selected biological warfare agents using tandem mass spectrometry

Elucidation of protein biomarkers for verification of selected biological warfare agents using tandem mass spectrometry

Francisella tularensis Periprosthetic Joint Infections Diagnosed with Growth in Cultures

Erreurs d'identification des agents biologiques à cote de sécurité élevée du groupe de risque 3 par SM MALDI-TOF au Canada : de novembre 2015 à octobre 2017

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