MALDI-TOF mass spectrometry applications in infectious diseases


Abstract

Background

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a powerful tool in the clinical microbiology laboratory, enabling accurate identification of bacteria, fungi, and mycobacteria grown in culture. First adopted in some European microbiology laboratories, its ease of use, accuracy, rapid turnaround time, and low cost have led to it becoming standard of care in clinical microbiology laboratories around the world.

Content

This chapter briefly discusses the history of MALDI-TOF MS leading to its commercialization and adoption in clinical microbiology laboratories. Identification of aerobic and anaerobic organisms, as well as mycobacteria and fungi, with a focus on the US Food and Drug administration (FDA)-approved/cleared platforms, is discussed. Additional applications, such as direct identification from blood cultures are reviewed as is implementation of MALDI-TOF MS into routine laboratory workflow.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Bacteria and other microorganisms have an abundance of unique proteins allowing for their taxonomic identification based on the mass “fingerprint” of their proteins. MALDI is considered a soft ionization technique with the matrix aiding in ionization of proteins without causing them to fragment when the laser is applied (see Chapter 20 ). Sample preparation is required before performing MALDI-TOF MS. Preparation entails applying a colony of bacteria onto a spot on the MALDI-TOF MS plate (with or without formic acid) or the more traditional method of using formic acid to disrupt the cells, followed by extraction of proteins with acetonitrile and then spotting onto a MALDI-TOF MS plate. The first method is used for routine identification of bacteria and yeast, with the latter typically reserved for difficult-to-lyse organisms. Direct colony processing is much simpler, requires less hands-on time, and is less expensive to perform than off-plate extraction. Other methods of preparation are used for processing liquid cultures because of the need of a purification step. Purification may be accomplished by filtering out impurities, or pelleting microbial cells via centrifugation, combined with repeated washings. An example of a common application of preparation from liquid cultures is the processing of positive blood cultures, discussed later in this chapter.

For direct colony processing, a colony is first “picked” from a culture plate and then spotted onto a position on a MALDI-TOF MS plate ( Fig. 22.1 ). Plates can be reusable (made of metals) or disposable and come in multiple configurations. The two common commercial systems worldwide are the MALDI Biotyper (Bruker Daltonics, Billerica, Massachusetts) and VITEK MS (bioMérieux, SA, Marcy-l’Etoile, France), although, as discussed later in the chapter, other systems are available. Formic acid may be added to improve the quality of the generated mass spectra, a method referred to as extended direct transfer or on plate formic acid testing (compared with direct testing where formic acid is not used). The spot (either the microbial mass alone or following drying of formic acid for the extended direct transfer method) is overlaid with matrix (typically α-cyano-4-hydroxycinnamic acid dissolved in an acidified mixture of organic solvents and water). A third approach involves a traditional extraction methodology with inactivation by ethanol followed by a pelleting step. The pellet is then suspended in formic acid followed by addition of acetonitrile. The suspension is then centrifuged and the supernatant spotted on the plate. Once dried, the spot is overlaid with matrix as with the direct or extended direct transfer methods. Once the matrix has dried, the plate is placed into the instrument.

FIGURE 22.1, Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) process. Using a plastic or wooden stick, loop, or pipette tip, a colony is picked from a culture plate to a spot on a MALDI-TOF MS target plate (a reusable or disposable plate with a number of test spots). One or many isolates may be tested at a time. In this example, cells are treated with formic acid on the target plate and then dried. The spot is then overlaid with matrix and dried. The plate is placed in the ionization chamber of the mass spectrometer (see Fig. 22.2 ). A mass spectrum is generated and compared against a database of mass spectra by the software, resulting in identification of the organism ( Candida parapsilosis in position A4 in the example).

After the plate is introduced to the ionization chamber, a pulsed laser is directed onto the matrix/analyte combination of each spot, causing desorption and ionization of microbial proteins and other molecules in a plume of ionized sample and matrix molecules. The matrix absorbs most of the energy from the laser, leading to an ionized state that transfers charge from matrix to proteins and other molecules through random molecular collisions. Ionized microbial proteins are accelerated in an electromagnetic field and enter a TOF mass analyzer maintained under vacuum in which proteins are separated based on their velocity, which is inversely proportional to their mass-to-charge (m/z) ratio. In the application discussed, the charge is most often +1. Finally, at the end of the flight tube, the ions hit an ion detector, with smaller proteins colliding with the ion detector first, followed by larger ones. The resulting time-resolved spectrum is eventually transformed to a mass spectrum by calibrating the system with peptides of known sizes, relating TOF to m/z . The resulting mass spectrum for a given sample microorganism is then compared with reference spectra of known microorganisms ( Fig. 22.2 ).

FIGURE 22.2, Matrix-assisted laser desorption/ionization time-of-flight (TOF) mass spectrometer. The target plate is placed into the chamber of the mass spectrometer. Spots to be analyzed are shot by a laser, desorbing and ionizing microbial and matrix molecules from the target plate. The cloud of ionized molecules is accelerated into the TOF mass analyzer, toward a detector. Lighter molecules travel faster, followed by progressively heavier analytes. A mass spectrum is generated, representing the number of ions hitting the detector over time. Separation is by mass-to-charge ratio, but because the charge is typically single for this application, separation is effectively by molecular weight.

History and development of commercial systems

The first proposal that mass spectrometry (MS) be used for identification of bacteria was in 1975, although the process proposed used an ionization method that fragmented proteins, thereby preventing effective analysis. The technology to study intact proteins by MS was not invented until the 1980s, when two groups developed similar ideas for detection of intact macromolecules. Koichi Tanaka and coworkers described use of an ultrafine metal powder mixed with glycerin to detect macromolecules without fragmentation, for which Tanaka was awarded the Nobel Prize in chemistry (shared with John Fenn and Kurt Wüthrich). Around the same time that Tanaka published his research, Franz Hillenkamp and Michael Karas published their work on soft desorption/ionization using an organic compound matrix, nicotinic acid, also allowing the analysis of large biomolecules ; the term matrix-assisted laser desorption/ionization (MALDI) was coined from this work. Over the past few decades, computer science, information technology, and aggregation of comprehensive databases of well-characterized reference spectra have led to MALDI-TOF MS becoming a standard method used in clinical microbiology laboratories. The two commercial systems mentioned earlier have been cleared by the US Food and Drug Administration (FDA) for routine identification of bacteria and fungi in clinical microbiology laboratories. Other platforms include the recently developed MicroIDSys (ASTA, Suwon, Korea), and the Chinese platforms Clin-TOF (Yixin, Beijing), Autof ms1000 (Autobiio, Henan) and microTyper MS (Tianru, Jiangsu); these will not be mentioned further. The VITEK MS (bioMérieux) and MALDI Biotyper CA System (Bruker Daltonics) have been approved/cleared by the FDA for identification of bacteria and fungi cultured on solid media. A list of claimed organisms as of December 1, 2019 is shown in Box 22.1 . Each system consists of a mass spectrometer, software, and a database; however, differences exist in each of the three components, as well as the organisms approved/cleared by the FDA for identification. Differences also exist in the size of the instruments; Bruker’s mass spectrometer is a bench-top model, and bioMérieux’s is a floor model instrument similar in size to a vending machine.

BOX 22.1
Reportable Organisms for the US Food and Drug Administration–approved/Cleared VITEK Mass Spectrometry and Bruker Matrix-assisted Laser Desorption/Ionization Biotyper CA Systems

Aerobic gram-positive bacteria

  • Abiotrophia defectiva V

  • Aerococcus sanguinicola B

  • Aerococcus urinae B

  • Aerococcus viridans

  • Alloiococcus otitis B

  • Arthrobacter cumminsii B

  • Brevibacterium casei B

  • Corynebacterium accolens B

  • Corynebacterium afermentans group B

  • Corynerbacterium afermentans

  • Corynebacterium pilbarense

  • Corynebacterium amycolatum B

  • Corynebacterium aurimucosum group B

  • Corynebacterium aurimucosum

  • Corynebacterium singulare

  • Corynebacterium bovis B

  • Corynebacterium coyleae B

  • Corynebacterium diphtheriae B

  • Corynebacterium freneyi B

  • Corynebacterium glucuronolyticium B

  • Corynebacterium glutamicum B

  • Corynebacterium jeikeium V

  • Corynebacterium kroppenstedtii B

  • Corynebacterium macginleyi B

  • Corynebacterium minutissimum B

  • Corynebacterium mucifaciens/ureicelerivorans group B

  • Corynebacterium mucifaciens

  • Corynebacterium ureicelerivorans

  • Corynebacterium propinquum B

  • Corynebacterium pseudodiphtheriticum B

  • Corynebacterium pseudotuberculosis B

  • Corynebacterium resistens B

  • Corynebacterium riegelii B

  • Corynebacterium striatum group B

  • Corynebacterium tuberculostearicum B

  • Corynebacterium ulcerans B

  • Corynebacterium urealyticum B

  • Corynebacterium xerosis B

  • Corynebacterium striatum group B

  • Corynebacterium striatum

  • Corynebacterium simulans

  • Curtobacterium flaccumfaciens V

  • Dermabacter hominis B

  • Dermacoccus nishinomiyaensis B

  • Enterococcus avium

  • Enterococcus casseliflavus

  • Enterococcus durans

  • Enterococcus faecalis

  • Enterococcus faecium

  • Enterococcus gallinarum

  • Enterococcus hirae

  • Enterococcus mundtii B

  • Enterococcus raffinosus B

  • Gardnerella vaginalis

  • Gemella haemolysans

  • Gemella morbillorum

  • Gemella sanguinis B

  • Granulicatella adiacens

  • Helcococcus kunzii B

  • Kocuria kristinae B

  • Kocuria rhizophila V

  • Kytococcus sedentarius B

  • Lactobacillus gasseri B

  • Lactobacillus jensenii B

  • Lactobacillus rhamnosus B

  • Lactococcus garvieae

  • Lactococcus lactis

  • Leuconostoc citreum B

  • Leuconostoc mesenteroides

  • Leuconostoc pseudomesenteroides

  • Listeria monocytogenes

  • Macrococcus caseolyticus B

  • Micrococcus luteus

  • Micrococcus lylae B

  • Nocardia abscessus V

  • Nocardia africana/nova V

  • Nocardia asteroides V

  • Nocardia brasiliensis

  • Nocardia cyriacigeorgica

  • Nocardia farcinica V

  • Nocardia farcinica group B

  • Nocardia farcinica

  • Nocardia kroppenstedtii

  • Nocardia nova B

  • Nocardia otitidiscaviarum

  • Nocardia paucivorans V

  • Nocardia pseudobrasiliensis V

  • Nocardia transvalensis V

  • Nocardia veterana V

  • Nocardia wallacei V

  • Pediococcus acidilactici

  • Pediococcus pentosaceus B

  • Rothia aeria B

  • Rothia dentocariosa B

  • Rothia mucilaginosa

  • Staphylococcus aureus

  • Staphylococcus auricularis

  • Staphylococcus capitis

  • Staphylococcus caprae B

  • Staphylococcus carnosus B

  • Staphylococcus chromogenes V

  • Staphylococcus cohnii B

  • Staphylococcus cohnii ssp. cohnii V

  • Staphylococcus cohnii ssp. urealyticus V

  • Staphylococcus delphini

  • Staphylococcus epidermidis

  • Staphylococcus equorum B

  • Staphylococcus felis B

  • Staphylococcus haemolyticus

  • Staphylococcus hominis

  • Staphylococcus hyicus V

  • Staphylococcus intermedius

  • Staphylococcus kloosii V

  • Staphylococcus lentus

  • Staphylococcus lugdunensis

  • Staphylococcus pasteuri B

  • Staphylococcus pettenkoferi B

  • Staphylococcus pseudintermedius

  • Staphylococcus saccharolyticus B

  • Staphylococcus saprophyticus

  • Staphylococcus schleiferi

  • Staphylococcus sciuri

  • Staphylococcus simulans

  • Staphylococcus vitulinus B

  • Staphylococcus warneri

  • Staphylococcus xylosus

  • Streptococcus agalactiae

  • Streptococcus alactolyticus V

  • Streptococcus anginosus

  • Streptococcus canis

  • Streptococcus constellatus

  • Streptococcus cristatus V

  • Streptococcus dysgalactiae B

  • Streptococcus dysgalactiae ssp. dysgalactiae V

  • Streptococcus dysgalactiae ssp. equisimilis V

  • Streptococcus equi B

  • Streptococcus equi ssp. equi V

  • Streptococcus equi ssp. zooepidemicus V

  • Streptococcus equinus

  • Streptococcus gallolyticus B

  • Streptococcus gallolyticus ssp. gallolyticus V

  • Streptococcus gallolyticus ssp. pasteurianus V

  • Streptococcus gordonii

  • Streptococcus infantarius ssp. coli (S. lutetiensis) V

  • Streptococcus infantarius ssp. infantarius V

  • Streptococcus intermedius

  • Streptococcus lutetiensis B

  • Streptococcus mitis/Streptococcus oralis V

  • Streptococcus mitis oralis group B

  • Streptococcus mitis

  • Streptococcus oralis

  • Streptococcus australis

  • Streptococcus cristatus

  • Streptococcus dentisani

  • Streptococcus infantis

  • Streptococcus oligofermentans

  • Streptococcus pseudopneumoniae

  • Streptococcus rubneri

  • Streptococcus sanguinis

  • Streptococcus tigu rinus

  • Streptococcus mutans

  • Streptococcus parasanguinis

  • Streptococcus pneumoniae

  • Streptococcus pseudoporcinus V

  • Streptococcus pyogenes

  • Streptococcus salivarius/vestibularis group

  • Streptococcus salivarius

  • Streptococcus vestribularis

  • Streptococcus salivarius ssp. salivarius V

  • Streptococcus sanguinis

  • Streptococcus sobrinus

  • Streptococcus suis V

  • Streptococcus thermophilus B

  • Streptococcus uberis V

  • Streptococcus vestibularis V

  • Trueperella bernardiae B

  • Turicella otitidis B

  • Vagococcus fluvialis B

Gram-negative bacteria, enterobacterales

  • Cedecea davisae V

  • Cedecea lapagei V

  • Cedecea neteri V

  • Citrobacter amalonaticus V

  • Citrobacter amalonaticus complex B

  • Citrobacter amalonaticus

  • Citrobacter farmeri

  • Citrobacter braakii V

  • Citrobacter farmeri V

  • Citrobacter freundii V

  • Citrobacter freundii complex B

  • Citrobacter braakii

  • Citrobacter freundii

  • Citrobacter gillenii

  • Citrobacter murliniae

  • Citrobacter rodentium

  • Citrobacter sedlakii

  • Citrobacter werkmanii

  • Citrobacter youngae

  • Citrobacter koseri

  • Citrobacter youngae V

  • Cronobacter muytjensii V

  • Cronobacter sakazakii V

  • Cronobacter sakazakii group B

  • Cronobacter sakazakii

  • Cronobacter dubliniensis

  • Cronobacter muytjensii

  • Cronobacter turicensis

  • Cronobacter turicensis V

  • Edwardsiella hoshinae V

  • Edwardsiella tarda

  • Enterobacter aerogenes

  • Enterobacter amingenus B

  • Enterobacter asburiae V

  • Enterobacter cancerogenus V

  • Enterobacter cloacae V

  • Enterobacter cloacae complex B

  • Enterobacter asburiae

  • Enterobacter cancerogenus

  • Enterobacter cloacae

  • Enterobacter hormaechi

  • Enterobacter kobei

  • Enterobacter ludwigii

  • Enterobacter gergoviae V

  • Enterobacter hormaechei V

  • Enterobacter kobei V

  • Enterobacter ludwigii V

  • Escherichia coli

  • Escherichia fergusonii V

  • Escherichia hermannii

  • Escherichia vluneris

  • Ewingella americana

  • Hafnia alvei

  • Klebsiella oxytoca V

  • Klebsiella oxytoca/Raoultella ornithinolytica B

  • Klebsiella pneumoniae

  • Klebsiella variicola

  • Kluyvera ascorbata V

  • Kluyvera cryocrescens V

  • Kluyvera intermedia V

  • Leclercia adecarboxylata

  • Lelliottia amnigena V

  • Morganella morganii

  • Pantoea agglomerans

  • Plesiomonas shigelloides B

  • Pluralibacter georgoviae

  • Proteus mirabilis

  • Proteus penneri V

  • Proteus vulgaris V

  • Proteus vulgaris group B

  • Proteus hauseri

  • Proteus penneri

  • Proteus vulgaris

  • Providencia alcalifaciens V

  • Providencia rettgeri

  • Providencia rustigianii V

  • Providencia stuartii

  • Raoultella ornithinolytica V

  • Raoultella planticola V

  • Raoultella terrigena V

  • Salmonella enterica ssp. enterica V

  • Salmonella sp. B

  • Serratia ficaria V

  • Serratia fonticola

  • Serratia grimesii V

  • Serratia liquefaciens

  • Serratia marcescens

  • Serratia odorifera

  • Serratia plymuthica

  • Serratia proteamaculans V

  • Serratia quinivorans V

  • Serratia rubidaea

  • Yersinia aldovae V

  • Yersinia enterocolitica

  • Yersinia frederiksenii

  • Yersinia intermedia

  • Yersinia kristensenii

  • Yersinia pseudotuberculosis

  • Yersinia ruckeri V

Gram-negative bacteria, non-enterobacterales

  • Achromobacter denitrificans V

  • Achromobacter xylosoxidans

  • Acinetobacter baumannii V

  • Acinetobacter baumannii/nosocomialis group B

  • Acinetobacter baumannii

  • Acinetobacter nosocomialis

  • Acinetobacter calcoaceticus

  • Acinetobacter haemolyticus

  • Acinetobacter johnsonii

  • Acinetobacter junii

  • Acinetobacter lwoffi

  • Acinetobacter nosocomialis V

  • Acinetobacter pittii

  • Acinetobacter radioresistens B

  • Acinetobacter ursingii B

  • Actinotignum schaalii group

  • Actinotignum schaali

  • Actinotignum sanguinis

  • Aeromonas hydrophila V

  • Aeromonas hydrophila/caviae group

  • Aeromonas allosaccharophila

  • Aeromonas aquariorum

  • Aeromonas caviae

  • Aeromonas culicicola

  • Aeromonas enteropelogenes

  • Aeromonas fluvialis

  • Aeromonas hydrophila

  • Aeromonas icthiosmia

  • Aeromonas jandaei

  • Aeromonas media

  • Aeromonas punctate

  • Aeromonas rivuli

  • Aeromonas sanarellii

  • Aeromonas sobria

  • Aeromonas taiwanensis

  • Aeromonas veronii

  • Aeromonas jandaei V

  • Aeromonas punctata (caviae) V

  • Aeromonas salmonicida

  • Aeromonas sobria V

  • Aeromonas veronii V

  • Alcaligenes faecalis B

  • Alcaligenes faecalis ssp. faecalis V

  • Bordetella avium V

  • Bordetella bronchiseptica V

  • Bordetella pertussis/bronchiseptica/parapertussis B

  • Bordetella hinzii B

  • Bordetella parapertussis V

  • Bordetella pertussis V

  • Brevundimonas diminuta V

  • Brevundimonas diminuta group B

  • Brevundimonas diminuta

  • Brevundimonas naejangsanensis

  • Brevundimonas vesicularis V

  • Burkholderia cenocepacia V

  • Burkholderia cepacia V

  • Burkholderia cepacia complex B

  • Burkholderia ambifaria

  • Burkholderia anthina

  • Burkholderia cenocepacia

  • Burkholderia cepacia

  • Burkholderia diffusa

  • Burkholderia dolosa

  • Burkholderia lata

  • Burkholderia latens

  • Burkholderia metallica

  • Burkholderia pyrrocina

  • Burkholderia seminalis

  • Burkholderia stabilis

  • Burkholderia vietnamiensis

  • Burkholderia contaminans V

  • Burkholderia gladioli B

  • Burkholderia multivorans

  • Burkholderia vietnamiensis V

  • Capnocytophaga ochracea B

  • Capnocytophaga sputigena B

  • Chryseobacterium gleum

  • Chryseobacterium indologenes

  • Comamonas testosteroni V

  • Cupriavidus pauculus group B

  • Cupriavidus pauculus

  • Cupriavidus metallidurans

  • Delftia acidovorans V

  • Delftia acidovorans group B

  • Delftia acidovorans

  • Delftia lacustris

  • Delftia litopenaei

  • Delftia tsuruhatensis

  • Elizabethkingia anophelis V

  • Elizabethkingia meningoseptica V

  • Elizabethkingia meningoseptica group B

  • Elizabethkingia meningoseptica

  • Elizabethkingia anopheles

  • Elizabethkingia miricola

  • Elizabethkingia miricola V

  • Mannheimia haemolytica V

  • Mannheimia haemolytica group B

  • Mannheimia haemolytica

  • Mannheimia glucosida

  • Myroides odoratimimus B

  • Myroides odoratus B

  • Myroides sp. V

  • Ochrobactrum anthropi V

  • Pantoea dispersa V

  • Pasteurella aerogenes V

  • Pasteurella multocida

  • Pseudomonas aeruginosa

  • Pseudomonas alcaligenes V

  • Pseudomonas fluorescens V

  • Pseudomonas fluorescens group B

  • Pseudomonas azotoformans

  • Pseudomonas brenneri

  • Pseudomonas cedrina

  • Pseudomonas congelans

  • Pseudomonas extremorientalis

  • Pseudomonas fluorescens

  • Pseudomonas gessardii

  • Pseudomonas libanensis

  • Pseudomonas mandelii

  • Pseudomonas marginalis

  • Pseudomonas migulae

  • Pseudomonas mucidolens

  • Pseudomonas orientalis

  • Pseduomonas poae

  • Pseudomonas rhodesiae

  • Pseudomonas synxantha

  • Pseudomonas tolaasii

  • Pseudomonas trivialis

  • Pseudomonas veronii

  • Pseudomonas luteola V

  • Pseudomonas mendocina V

  • Pseudomonas oryzihabitans

  • Pseudomonas putida V

  • Pseudomonas putida group B

  • Pseudomonas fulva

  • Pseudomonas monteilii

  • Pseudomonas mosselii

  • Pseudomonas plecoglossicida

  • Pseudomonas putida

  • Pseudomonas stutzeri

  • Ralstonia pickettii

  • Rhizobium radiobacter

  • Shewanella putrefaciens V

  • Sphingobacterium multivorum

  • Sphingobacterium spiritivorum

  • Sphingomonas paucimobilis V

  • Sphingomonas paucimobilis group B

  • Sphingomonas paucimobilis

  • Sphingomonas zeae

  • Stenotrophomonas maltophilia

  • Sutterella wadsworthensis B

  • Vibrio alginolyticus V

  • Vibrio cholerae V

  • Vibrio fluvialis V

  • Vibrio metschnikovii V

  • Vibrio mimicus V

  • Vibrio parahaemolyticus

  • Vibrio vulnificus

Fastidious gram-negative bacteria

  • Aggregatibacter actinomycetemicomitans

  • Aggregatibacter aphrophilus

  • Aggregatibacter segnis

  • Brucella sp. V

  • Campylobacter coli

  • Camplylobacter jejuni

  • Campylobacter rectus V

  • Campylobacter ureolyticus B

  • Eikenella corrodens

  • Fluoribacter bozemanae

  • Haemophilus haemolyticus B

  • Haemophilus influenzae

  • Haemophilus parahaemolyticus V

  • Haemophilus parahaemolyticus group B

  • Haemophilus parahaemolyticus

  • Haemophilus paraphrohaemolyticus

  • Haemophilus parainfluenzae

  • Kingella denitrificans

  • Kingella kingae

  • Legionella longbeachae B

  • Legionella pneumophila V

  • Moraxella catarrhalis

  • Moraxella lacunata V

  • Moraxella nonliquefaciens

  • Moraxella osloensis

  • Neisseria bacilliformis B

  • Neisseria cinerea

  • Neisseria elongota

  • Neisseria flavescens/subflava group B

  • Neisseria flavescens

  • Neisseria perflava

  • Neisseria subflava

  • Neisseria gonorrhoeae

  • Neisseria lactamica B

  • Neisseria meningitidis

  • Neisseria mucosa/sicca V

  • Neisseria sicca group B

  • Neisseria macacae

  • Neisseria mucosa

  • Neisseria sicca

  • Neisseria weaveri

  • Oligella ureolytica

  • Oligella urethralis

  • Weeksella virosa

Anaerobic bacteria

  • Actinomyces bovis V

  • Actinomyces europaeus B

  • Actinomyces funkei B

  • Actinomyces graevenitzii B

  • Actinomyces hyovaginalis B

  • Actinomyces israelii V

  • Actinomyces meyeri

  • Actinomyces naeslundii V

  • Actinomyces neuii

  • Actinomyces odontolyticus

  • Actinomyces oris B

  • Actinomyces radingae B

  • Actinomyces turicensis B

  • Actinomyces urogenitalis B

  • Alloscardovia omnicolens B

  • Anaerococcus murdochii B

  • Anaerococcus vaginalis B

  • Bacteroides caccae

  • Bacteroides eggerthii V

  • Bacteroides fragilis

  • Bacteroides nordii

  • Bacteroides ovatus/xylanisolvens V

  • Bacteroides ovatus group B

  • Bacteroides ovatus

  • Bacteroides xylanisolvens

  • Bacteroides pyogenes

  • Bacteroides salyesiae B

  • Bacteroides stercoris V

  • Bacteroides stercoris group B

  • Bacteroides stercoris

  • Bacteroides eggerthii

  • Bacteroides thetaiotaomicron V

  • Bacteroides thetaiotaomicron group B

  • Bacteroides thetaiotaomicron

  • Bacteroides faecis

  • Bacteroides uniformis

  • Bacteroides vulgatus

  • Bacteroides vulgatus group B

  • Bacteroides vulgatus

  • Bacteroides dorei

  • Bifidobacterium breve B

  • Bifidobacterium sp. V

  • Biolphila wadsworthia V

  • Clostridium baratii V

  • Clostridium beijerinckii

  • Clostridium bifermentans B

  • Clostridium butyricum

  • Clostridium cadaveris V

  • Clostridium clostridioforme V

  • Clostridium clostridioforme group B

  • Clostridium clostridioforme

  • Clostridium bolteae

  • Clostridioides difficile

  • Clostridium innocuum

  • Clostridium novyi V

  • Clostridium paraputrificum B

  • Clostridium perfringens

  • Clostridium ramosum

  • Clostridium septicum

  • Clostridium sordellii B

  • Clostridium sporogenes V

  • Clostridium sporogenes/Clostridium botulinium (group I) B

  • Clostridium tertium

  • Clostridium tetani V

  • Cutibacterium acnes

  • Cutibacterium avidum V

  • Cutibacterium granulosum V

  • Facklamia hominis B

  • Finegoldia magna

  • Fusobacterium canifelinum B

  • Fusobacterium mortiferum V

  • Fusobacterium necrophorum

  • Fusobacterium nucleatum

  • Fusobacterium periodonticum V

  • Hathewaya histolytica V

  • Mobiluncus curtisii

  • Paenclostridium sordellii V

  • Parabacteroides distasonis B

  • Parabacteroides goldsteinii B

  • Parabacteroides johnsonii/merdae group B

  • Parabacteroides johnsonii

  • Parabacteroides merdae

  • Paraclostridium bifermentans V

  • Parvimonas micra V

  • Peptoniphilus asaccharolyticus V

  • Peptoniphilus harei group B

  • Peptoniphilus harei

  • Peptoniphilus inodolicus

  • Peptostreptococcus anaerobius

  • Porphyromonas asaccharolytica/uenonis V

  • Porphyromonas gingivalis

  • Porphyromonas somerae B

  • Prevotella bivia

  • Prevotella buccae

  • Prevotella denticola

  • Prevotella intermedia

  • Prevotella loescheii V

  • Prevotella melaninogenica

  • Prevotella oralis V

  • Prevotella oris V

  • Propionibacterium acidipropionici V

  • Propionibacterium propionicum V

  • Tannerella forsythia V

  • Veillonella dispar V

  • Veillonella parvula group B

  • Veillonella parvula

  • Veillonella dispar

  • Veillonella rugosae

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