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Department of Clinical Microbiology, Complejo Asistencial Universitario de León, calle Altos de Nava, s/n, 24080 León, SpainInstitute of Biomedicine (IBIOMED), León, Spain
The taxonomy, microbiology, and identification of Corynebacterium kroppenstedtii are reviewed and updated.
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All published isolations of C. kroppenstedtii are reviewed and analyzed.
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A comprehensive review of human and animal infections is presented.
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The possible role of C. kroppenstedtii in granulomatous mastitis is discussed.
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Antibiotic susceptibility data and detected resistance genes are given and reviewed.
Summary
The genus Corynebacterium represents a taxon of Gram-positive bacteria with a high G + C content in the genomic DNA. Corynebacterium kroppenstedtii is an unusual member of this taxon as it lacks the characteristic mycolic acids in the cell envelope. Genome sequence analysis of the C. kroppenstedtii type strain has revealed a lipophilic (lipid-requiring) lifestyle and a remarkable repertoire of carbohydrate uptake and utilization systems. Clinical isolates of C. kroppenstedtii have been obtained almost exclusively from female patients and mainly from breast abscesses and cases of granulomatous mastitis. However, the role of C. kroppenstedtii in breast pathologies remains unclear. This review provides a comprehensive overview of the taxonomy, microbiology, and microbiological identification of C. kroppenstedtii, including polyphasic phenotypic approaches, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the use of 16S rRNA gene sequencing. A clinical review presents reported cases, various antimicrobial treatments, antibiotic susceptibility assays, and antibiotic resistance genes detected during genome sequencing. C. kroppenstedtii must be considered a potential opportunistic human pathogen and should be identified accurately in clinical laboratories.
The genus Corynebacterium currently comprises almost 100 species and represents a very diverse collection of taxonomically related Gram-positive bacteria (http://www.bacterio.net).
in: Whitman W.B. Goodfellow M. Kämpfer P. Busse H.J. Trujillo M.E. Ludwig W. Bergey's manual of systematic bacteriology. Volume 5: Actinobacteria. Springer,
New York2012: 245-289
The detection of corynebacteria in various habitats of the human body has broadened in recent years as a result of culture-independent approaches and the application of next-generation DNA sequencing technologies.
These studies have provided vast sets of 16S rRNA gene sequences, and through this, a compilation of the bacterial repertoire that is associated with human beings as commensals or pathogens.
Developments in technology have recently led to the generation of three-dimensional maps of the chemical makeup of the human skin surface, with correlation to the bacteria of the skin microbiome .
Corynebacterium species of the human microbiome have often been assigned as opportunistic pathogens, as they have rarely been associated with human infections and have been regarded as contaminants in clinical specimens.
Nevertheless, several coryne-bacteria have been implicated in human disease. The closely related species Corynebacterium diphtheriae and Corynebacterium ulcerans, for instance, may produce potent exotoxins, which play significant roles in pathogenicity,
Corynebacterium kroppenstedtii is a true member of the genus Corynebacterium, but it lacks the typical mycolic acids of the cell envelope. It was first isolated in 1998 from a human sputum sample,
and has since occasionally been associated with human infections, mainly breast abscesses and granulomatous mastitis. Information on the pathogenicity and antimicrobial susceptibility of C. kroppenstedtii is relatively scant. This review provides an overview of the taxonomy and microbiology of C. kroppenstedtii and summarizes reported cases of C. kroppenstedtii isolation from clinical specimens. Most C. kroppenstedtii isolates have been obtained from breast samples. By reviewing all published cases, a possible association with breast abscesses and granulomatous mastitis was sought–an association that needs stronger medical evidence.
2. Species description
2.1 Taxonomy of C. kroppenstedtii
C. kroppenstedtii has been classified by chemotaxonomic data as a member of the genus Corynebacterium.
in: Whitman W.B. Goodfellow M. Kämpfer P. Busse H.J. Trujillo M.E. Ludwig W. Bergey's manual of systematic bacteriology. Volume 5: Actinobacteria. Springer,
New York2012: 245-289
According to recent taxonomic changes, this genus is part of the family Corynebacteriaceae, order Corynebacteriales, class Actinobacteria, phylum Actinobacteria.
Corynebacteriaceae Lehmann and Neumann 1907AL emend. Stackebrandt, Rainey and Ward-Rainey 1997, 485 emend. Zhi, Li, Stackebrandt 2009, 593.
in: Whitman W.B. Goodfellow M. Kämpfer P. Busse H.J. Trujillo M.E. Ludwig W. Bergey's manual of systematic bacteriology. Volume 5: Actinobacteria. Springer,
New York2012: 244-245
in: Whitman W.B. Goodfellow M. Kämpfer P. Busse H.J. Trujillo M.E. Ludwig W. Bergey's manual of systematic bacteriology. Volume 5: Actinobacteria. Springer,
New York2012: 34-35
in: Whitman W.B. Goodfellow M. Kämpfer P. Busse H.J. Trujillo M.E. Ludwig W. Bergey's manual of systematic bacteriology. Volume 5: Actinobacteria. Springer,
New York2012: 235-243
This phylum is composed mainly of Gram-positive bacteria with a high G + C content in the genomic DNA and exhibits enormous diversity in terms of morphology, physiology, and metabolic capabilities. The order Corynebacteriales represents one of the largest groups within the actinobacteria in terms of the number of species that have been validly published. The species of this order are characterized by cell wall chemotype IV, which is defined by the presence of meso-diaminopimelic acid, arabinose, and galactose in the cell wall, and by the presence of mycolic acids that are an important component of the cell envelope. Most Corynebacterium species contain mycolic acids with 22 - 36 carbons, although ranges of 20 − 38 carbons have also been detected.
Species lacking mycolic acids are Corynebacterium amycolatum, Corynebacterium caspium, Corynebacterium ciconiae, Corynebacterium lactis, and C. kroppenstedtii.
According to genome sequence data, the lack of mycolic acids in C. kroppenstedtii may be caused by gene loss, comprising at least a condensase gene region and a mycolate reductase gene, both contributing to the biosynthesis of mycolic acids in other corynebacteria.
Ultrafast pyrosequencing of Corynebacterium kroppenstedtii DSM44385 revealed insights into the physiology of a lipophilic Corynebacterium that lacks mycolic acids.
The phylogenetic relationship of C. kroppenstedtii with other Corynebacterium species can be deduced from dendrograms that generally derive from the alignment of the 16S rRNA or rpoB gene sequences.
The rpoB gene sequence of corynebacteria allows accurate species identification, as it is significantly more polymorphic than the 16S rRNA gene. Phylogenetic analysis on the basis of rpoB gene sequence alignment has revealed four clusters in the genus Corynebacterium with a reliable taxonomic organization supported by high bootstrap values.
C. kroppenstedtii has been assigned as a deeply branching node to cluster 3 of the genus Corynebacterium, along with Corynebacterium jeikeium, C. urealyticum, and others. In phylogenetic trees based on alignment of partial 16S rRNA gene sequences, C. kroppenstedtii forms a distinct clade with the same taxonomic relatives.
This taxonomic grouping is, moreover, supported by molecular markers of conserved signature indels (CSIs) of defined lengths that are present in gene or protein sequences at specific positions and that are uniquely shared by particular groups of organisms. One example of a corynebacterial conserved signature indel is an insert of seven to eight amino acids in a conserved region of the β′ subunit of RNA polymerase (RpoC) that is generally present in subclade I of Corynebacterium species, but that is not found in C. jeikeium, C. urealyticum, C. kroppenstedtii, and other corynebacteria that are not part of this subclade.
In addition it has to be noted that other CSIs specific for subclade I species or for C. jeikeium and C. urealyticum are not present in C. kroppenstedtii. The absence of CSIs for the other two corynebacterial clades in C. kroppenstedtii suggests that this species forms a distinct evolutionary subgroup in the genus Corynebacterium.
C. kroppenstedtii was first described in 1998 by Collins et al. who isolated this bacterium from the sputum of an 82-year-old female with pulmonary disease.
The type strain of this species is represented by the clinical isolate CCUG 35717 (CIP 105744, DSM 44385, JCM11950). The cells are Gram-positive, non-motile, non-spore-forming, non-pigmented, rod-shaped diphtheroids with typical coryneform morphology. Colonies on blood agar are non-pigmented to greyish, matt, smooth, round, convex, less than 1 mm in diameter after 24 h of incubation, and non-haemolytic (Fig. 1).
Fig. 1Corynebacterium kroppenstedtii: (a) Gram stain; (b) subculture on sheep blood agar after 24 h of incubation in aerobic conditions; (c) subculture on sheep blood agar after 72 h of incubation in aerobic conditions; (d) subculture on sheep blood agar after 24 h of incubation in aerobic conditions–one drop of Tween 80 was added to the lower third part of the Petri dish.
acid is produced from glucose, maltose, and sucrose, but not from lactose, mannitol, glycogen, ribose, or d-xylose. Hydrolysis of aesculin is positive. Some clinical isolates can produce propionic acid as a metabolic product.
Positive biochemical reactions are detected for leucine arylamidase, esterase C4, ester lipase C8, and pyrazinamidase; negative reactions for alkaline and acid phosphatases, N-acetyl-β-glucosaminidase, cystine arylamidase, chymotrypsin, α-fucosidase, α-galactosidase, β-galactosidase, α-glucosidase, β-glucosidase, β-glucuronidase, lipase C14, α-mannosidase, pyrrolidonyl arylamidase, trypsin, and valine arylamidase. Nitrate is not reduced to nitrite; urea is not hydrolyzed. The major long-chain cellular fatty acids are C16:0, C18:0, and C18:1ω9. Tuberculostearic acid is present. The DNA base composition of the type strain CCUG 35717 is 62 mol% G + C.
this metabolic feature was observed in a later study as colonies grew poorly on sheep blood agar but well on the same medium supplemented with 1% Tween 80,
as well as in brain‐heart infusion broth with Tween 80 (Fig. 2). Lipophilism as a metabolic feature of C. kroppenstedtii has also been deduced from the annotation of the genome sequence of the type strain.
Ultrafast pyrosequencing of Corynebacterium kroppenstedtii DSM44385 revealed insights into the physiology of a lipophilic Corynebacterium that lacks mycolic acids.
The genome sequencing project suggested that the lipophilic lifestyle of C. kroppenstedtii is caused by gene loss, comprising the fatty acid synthase gene. This evolutionary event of gene loss is also detectable in the close taxonomic relatives of corynebacterial cluster 3, C. jeikeium, C. urealyticum, Corynebacterium bovis, and Corynebacterium resistens.
Fig. 2Corynebacterium kroppenstedtii: subculture in brain‐heart infusion broth (left tube) and brain‐heart infusion broth enriched with 1% Tween 80 (right tube) after 24 h.
2.3 Microbiological identification of C. kroppenstedtii
Accurate microbiological identification of C. kroppenstedtii isolates can be achieved in the clinical laboratory by a combination of standard biochemical methods. C. kroppenstedtii can be distinguished from other corynebacteria lacking the characteristic mycolic acids by several biochemical characteristics (Table 1). API Coryne (bioMérieux, Marcy l'Etoile, France) in its different versions has been used by many authors.
In principle, API Coryne is a useful tool to complement homemade biochemical tests, but it is not suitable to identify C. kroppenstedtii as this species is not included in the respective database. In a few reports in which API Coryne profiling was performed, initially doubtful identifications as Propionibacterium acnes
have been suggested. Bernard et al. described API profiles of 2040104 (sucrose-negative) and 2040105 (sucrose-positive) for two isolates that were both aesculin-positive by API Coryne system but negative in other media.
The present authors isolated two strains associated with granulomatous mastitis with API profiles of 2100104 (maltose, sucrose, and aesculin-negative) after 24 h and 2140104 (maltose and sucrose-negative, aesculin-positive) after 48 h.
Table 1Biochemical characteristics to distinguish Corynebacterium kroppenstedtii from other corynebacteria lacking mycolic acids
The results of biochemical tests should be reported stating the media used and time of incubation, as acid production from carbohydrates and aesculin hydrolysis might be delayed in many organisms. This is particularly important in lipophilic corynebacteria for which an inoculum of ≥6 McFarland standard turbidity must be carefully prepared.
Moreover, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), mainly based on Bruker systems, has been established for the identification of clinical Corynebacterium species and has since successfully complemented classical biochemical approaches.
Formic acid-based direct, on-plate testing of yeast and Corynebacterium species by Bruker Biotyper matrix-assisted laser desorption ionization-time of flight mass spectrometry.
Using MALDI-TOF MS as described previously, the two coryneform isolates investigated by the present authors gave significant scores for C. kroppenstedtii of 1.990 and 1.780, values considered accurate enough for species identification.
Formic acid-based direct, on-plate testing of yeast and Corynebacterium species by Bruker Biotyper matrix-assisted laser desorption ionization-time of flight mass spectrometry.
Determination of the 16S rRNA gene sequences and of the hypervariable region of the rpoB gene are the reference methods for taxonomic identification of corynebacteria.
Cystic neutrophilic granulomatous mastitis: further characterization of a distinctive histopathologic entity not always demonstrably attributable to Corynebacterium infection.
were obtained from female patients. Thirty-seven isolates (88.0%) originated from breast clinical samples, two from sputum, and one each from lung biopsy, blood culture, and a prosthetic valve, the latter in a male patient. The final diagnosis in breast pathology cases was breast abscesses in 17 cases (45.9%), granulomatous mastitis in 13 cases (35.1%), suppurative lipogranuloma in two cases (5.4%), and mixed diagnosis in four cases (10.8%) (granulomatous mastitis plus breast abscess in three cases and granulomatous mastitis plus suppurative lipogranuloma in one case); a single case was without a diagnosis (2.7%). Breast abscesses occurred in patients in the age range of 22–57 years (mean 35.9 years) and granulomatous mastitis in patients of similar ages (20–47 years, mean 34.5 years). Data on parity were available for 18 women, being between 1 and 4 (mean 2.7) in patients with breast abscesses and between 0 and 3 (mean 1.6) in those with granulomatous mastitis.
Table 2Summary of data for 42 cases of Corynebacterium kroppenstedtii isolations from human clinical samples
Information on ethnicity was obtained for 12 cases of breast abscesses: three were Caucasian, two were Maori, two were Tongan, and two were Pacific Islander. Ethnicity was known for eight patients diagnosed with granulomatous mastitis: four were Caucasian, two were Maori, one was Samoan, and one was Japanese. Information on the type of specimen obtained was available for 24 cases, with pus predominating (16 cases), followed by biopsies (seven cases) and surgical drainage (two cases). For these specimens, information on the presence of inflammatory cells and Gram stain results was available for only 11 cases of breast abscesses. All cases showed polymorphonuclear cells, but Gram-positive bacteria were detected in only two cases (18.2%). Data for the cases of granulomatous mastitis showed the presence of polymorphonuclear cells in five out of the five cases and the presence of Gram-positive bacilli in two out of the seven cases (28.5%).
The role of C. kroppenstedtii in human mastitis and especially in granulomatous mastitis needs further investigation. There are reports of granulomatous mastitis where no organisms have been isolated.
Cystic neutrophilic granulomatous mastitis: further characterization of a distinctive histopathologic entity not always demonstrably attributable to Corynebacterium infection.
On the other hand, there are also cases probably associated with other Corynebacterium species, such as C. tuberculostearicum, C. amycolatum, C. glucuronolyticum, and C. freneyi.
Some reports do not provide sufficient information on the sample quality or on the number of microorganisms recovered. Frequently, bacteria were not visualized by Gram staining of the clinical samples. The possibility that C. kroppenstedtii was a secondary colonizer could not be completely ruled out in some of the published cases. However, as previously argued,
the corynebacterial organisms were frequently found in histological specimens of breast tissues and in granulomatous mastitis, surrounded by a granulomatous inflammatory reaction, and were observed relatively early in the clinical presentation. Moreover, it is well accepted that corynebacteria stain poorly in clinical samples.
Nevertheless, granulomatous mastitis is a very complex entity where the presence of C. kroppenstedtii could be just one piece of a yet unsolved puzzle.
A case of early prosthetic valve endocarditis in a 59-year-old male patient diagnosed by PCR and 16S rRNA gene sequencing was recently published;
this is the first case of this severe disease caused by C. kroppenstedtii to be described. Coryneforms, usually accompanied by polymorphonuclear cells, were seen on tissue smear preparations. The outcome was favourable after surgery and appropriate antimicrobial treatment. There is no clinical information available regarding the isolates obtained from a lung biopsy and a blood culture.
A case of otitis externa associated with C. kroppenstedtii has been described in a peach-faced lovebird that was treated successfully using topical antiseptics.
Treatment of otitis externa associated with Corynebacterium kroppenstedtii in a peach-faced lovebird (Agapornis roseicollis) with an acetic and boric acid commercial solution.
Information regarding the clinical outcomes in breast pathologies is generally scarce and the follow-up has been short in many cases. Nevertheless, most cases have involved a torpid and long-standing process, frequently of months and even years, with common recurrences of both breast abscesses and granulomatous mastitis. Regarding the treatment of cases associated with the detection of C. kroppenstedtii, surgery has been necessary in many cases of both breast abscesses and granulomatous mastitis, using multiple incision and drainage procedures. Antibiotics, often administered for long periods of time, have been associated with favourable outcomes. The most commonly used antimicrobials have been doxycycline, amoxicillin (with and without clavulanic acid), ciprofloxacin, and cefuroxime. Some reports have suggested that lipophilic antibiotics such as doxycycline, ciprofloxacin, and pristinamycin could be more effective for treating breast infections associated with this organism,
Antibiotics were not always prescribed for the treatment of granulomatous mastitis and when used there was insufficient information regarding doses and the duration of treatment. In some cases steroids were administered and surgical procedures varied making it very difficult to draw conclusions on the efficacy of each procedure. The use of steroids seems to be appropriate in cases of granulomatous mastitis.
Most importantly, no mortality has been reported for any of the cases listed in Table 2.
The case of prosthetic valve endocarditis by C. kroppenstedtii required extensive debridement to remove the abscess and infected tissue along with a sutureless valve implantation.
Empiric antimicrobial treatment with vancomycin, gentamicin, and rifampicin was initiated; this was changed to penicillin plus rifampicin when microbiological data were available, with a favourable outcome.
Treatment of otitis externa associated with Corynebacterium kroppenstedtii in a peach-faced lovebird (Agapornis roseicollis) with an acetic and boric acid commercial solution.
For antimicrobial susceptibility testing of corynebacteria, the broth microdilution technique in cation-adjusted Mueller–Hinton broth with lysed horse blood (2.5–5%) is recommended by the Clinical and Laboratory Standards Institute (CLSI), which has established susceptibility breakpoints for penicillin, vancomycin, gentamicin, and erythromycin.
Methods for antimicrobial dilution and disk susceptibility testing of infrequently isolated or fastidious bacteria; approved guideline—second edition M45-A2. Vol. 30, No. 18.
The European Committee on Antimicrobial Susceptibility Testing (EUCAST) also recommends the same technique, but has implemented a method for disk diffusion and defines susceptibility breakpoints for penicillin, ciprofloxacin, moxifloxacin, gentamicin, vancomycin, clindamycin, tetracycline, linezolid, and rifampicin.
Only a few clinical isolates of C. kroppenstedtii have been tested for antimicrobial susceptibility and most data have been obtained using the disk diffusion method,
Cystic neutrophilic granulomatous mastitis: further characterization of a distinctive histopathologic entity not always demonstrably attributable to Corynebacterium infection.
has been described. Even applying the rigorous criteria defined by EUCAST and using the Etest method, resistance to penicillin (91%), ciprofloxacin (18%), moxifloxacin (18%), and clindamycin (9%) has been reported.
The C. kroppenstedtii strain isolated from an endocarditis case was studied by disk susceptibility tests following the EUCAST methodology. This organism was regarded as susceptible to penicillin, clindamycin, rifampicin, moxifloxacin, vancomycin, and linezolid.
Minimum inhibitory concentrations (MICs) determined by Etest were also studied, being 0.023 mg/l for penicillin and 0.5 mg/l for daptomycin.
The present authors recently studied two clinical C. kroppenstedtii strains (ITA105 and ITA205) by Etest and found the following MICs, given in mg/l: penicillin (0.064/0.023), cefotaxime (0.047/0.023), imipenem (0.016/0.047), vancomycin (0.75/0.38), linezolid (0.064/0.064), daptomycin (0.094/0.25), tetracycline (1/32), ciprofloxacin (0.094/ > 32), erythromycin (<0.016/ > 256), clindamycin (0.032/ > 256), quinupristin/dalfopristin (0.38/ > 32), gentamicin (0.016/0.032), rifampicin (<0.002/ < 0.002), and co-trimoxazole (0.032/ > 32).
6. Genome sequences and antibiotic resistance
The application of ultra-fast and high-throughput DNA sequencing approaches, collectively named next-generation DNA sequencing technologies, has resulted in detailed insights into the genome architecture and the gene content of Corynebacterium species in recent years.
Prominent features of C. kroppenstedtii genomes are summarized in Table 3. In 2008, the complete genome sequence of the type strain C. kroppenstedtii DSM 44385 was published, along with a detailed annotation of the central carbon metabolism and the deduced lifestyle.
Ultrafast pyrosequencing of Corynebacterium kroppenstedtii DSM44385 revealed insights into the physiology of a lipophilic Corynebacterium that lacks mycolic acids.
The genome project revealed a large repertoire of genes involved in the uptake of various sugars, and consequently a complex central carbon metabolism.
Table 3Features of Corynebacterium kroppenstedtii genomes
In 2015, draft genome sequences of the antibiotic-sensitive strain C. kroppenstedtii ITA105 (CNM633/14) and the multidrug-resistant strain C. kroppenstedtii ITA205 (CNM632/14) were determined, both isolated from cases of granulomatous mastitis.
Draft genome sequences of Corynebacterium kroppenstedtii CNM633/14 and CNM632/14, multidrug-resistant and antibiotic-sensitive isolates from nodules of granulomatous mastitis patients.
The current three genome sequences show that the C. kroppenstedtii chromosome has a size range of 2.44 Mbp to 2.57 Mbp and a chromosomal G + C content ranging from 56.8% to 57.5%. The number of protein-coding genes predicted by bioinformatic methods is in the range of 2000 (Table 3).
The antibiotic resistance genes of the multidrug-resistant isolate CNM633/14 were allocated to a specific genomic island with significant similarity to the R plasmid pJA144188 of C. resistens DSM 45100.
Complete genome sequence, lifestyle, and multi-drug resistance of the human pathogen Corynebacterium resistens DSM 45100 isolated from blood samples of a leukemia patient.
The erm(X) gene encodes a 23S rRNA methyltransferase and confers cross-resistance in corynebacteria to many macrolides and lincosamides, including azithromycin, erythromycin, josamycin, midecamycin, roxithromycin, spiramycin, tylosin, clindamycin, and lincomycin, and to the streptogramin B antibiotics quinupristin and pristinamycin IA. The tet(W) gene confers cross-resistance to tetracycline and minocycline in corynebacteria by a ribosomal protection mechanism. Broad aminoglycoside resistance is mediated by the aphA1-IAB gene and the strA–strB gene pair. The former gene, encoding an aminoglycoside 3′-phosphotransferase, can provide resistance to kanamycin, neomycin, lividomycin, paromomycin, and ribostamycin in corynebacteria; the latter genes encode the enzymes aminoglycoside 3′′-phosphotransferase Ib and aminoglycoside 6-phosphotransferase Id and specifically confer streptomycin resistance. The cmx gene codes for an efflux protein of the major facilitator superfamily and is involved in chloramphenicol resistance, whereas the sul1 gene encodes a dihydropteroate synthase that can confer resistance to a broad spectrum of sulfonamides.
Complete genome sequence, lifestyle, and multi-drug resistance of the human pathogen Corynebacterium resistens DSM 45100 isolated from blood samples of a leukemia patient.
All except five reported C. kroppenstedtii strains have been isolated from the breasts of females, mostly from patients with breast abscesses and granulomatous mastitis. Approximately 50% of breast abscesses are caused by Staphylococcus aureus, but all other cases are produced by mixed anaerobes, anaerobic cocci, coagulase-negative staphylococci, and others.
Non-lactational cases are frequently recurrent and difficult to treat, as observed in cases where Corynebacterium species, including C. kroppenstedtii, have been involved. For these reasons, surgery and long courses of antibiotics are usually necessary to attain cure.
Granulomatous mastitis is an inflammatory breast disease thought to be of unknown aetiology that generally affects women of child-bearing age, usually within a few years after they have given birth.
The disease can become chronic and disfiguring and it can be confused with a tumour. Mammary granulomas have been associated with tuberculosis, sarcoidosis, fungal infections, and Wegener's granulomatosis, but since 2002 they have also been associated with infection by C. kroppenstedtii. The role of this organism as a cause or complicating factor of granulomatous mastitis has been demonstrated by several authors,
but further clinical and histopathological studies are necessary to clarify its real role in this disease. In many cases, long courses of antibiotics with or without surgery have been necessary for cure. A search for the best antimicrobial therapy should be carried out, taking into account the site where the infection occurs as well as host factors. Furthermore the ecology of this organism should be studied, as well as its microbiological features, in order to determine the unknown mechanisms of pathogenicity.
Acknowledgements
We thank D. Rodríguez-Lázaro (Universidad de Burgos, Spain), J.A. Sáez-Nieto and S. Valdezate (Instituto de Salud Carlos III, Madrid, Spain), M. Hernandez and J. Ariza-Miguel (Instituto Tecnológico Agrario de Castilla y León, Valladolid, Spain), and A. Acedo (AC-Gen Reading Life, Valladolid, Spain) for their contribution to the molecular and genetic characterization of our isolates. Part of this work has been supported by the Gerencia Regional de Salud, Junta de Castilla y León, Spain (research project GRS 698/A/2011).
in: Whitman W.B. Goodfellow M. Kämpfer P. Busse H.J. Trujillo M.E. Ludwig W. Bergey's manual of systematic bacteriology. Volume 5: Actinobacteria. Springer,
New York2012: 245-289
Corynebacteriaceae Lehmann and Neumann 1907AL emend. Stackebrandt, Rainey and Ward-Rainey 1997, 485 emend. Zhi, Li, Stackebrandt 2009, 593.
in: Whitman W.B. Goodfellow M. Kämpfer P. Busse H.J. Trujillo M.E. Ludwig W. Bergey's manual of systematic bacteriology. Volume 5: Actinobacteria. Springer,
New York2012: 244-245
in: Whitman W.B. Goodfellow M. Kämpfer P. Busse H.J. Trujillo M.E. Ludwig W. Bergey's manual of systematic bacteriology. Volume 5: Actinobacteria. Springer,
New York2012: 34-35
in: Whitman W.B. Goodfellow M. Kämpfer P. Busse H.J. Trujillo M.E. Ludwig W. Bergey's manual of systematic bacteriology. Volume 5: Actinobacteria. Springer,
New York2012: 235-243
Ultrafast pyrosequencing of Corynebacterium kroppenstedtii DSM44385 revealed insights into the physiology of a lipophilic Corynebacterium that lacks mycolic acids.
Formic acid-based direct, on-plate testing of yeast and Corynebacterium species by Bruker Biotyper matrix-assisted laser desorption ionization-time of flight mass spectrometry.
Cystic neutrophilic granulomatous mastitis: further characterization of a distinctive histopathologic entity not always demonstrably attributable to Corynebacterium infection.
Treatment of otitis externa associated with Corynebacterium kroppenstedtii in a peach-faced lovebird (Agapornis roseicollis) with an acetic and boric acid commercial solution.
Methods for antimicrobial dilution and disk susceptibility testing of infrequently isolated or fastidious bacteria; approved guideline—second edition M45-A2. Vol. 30, No. 18.
Draft genome sequences of Corynebacterium kroppenstedtii CNM633/14 and CNM632/14, multidrug-resistant and antibiotic-sensitive isolates from nodules of granulomatous mastitis patients.
Complete genome sequence, lifestyle, and multi-drug resistance of the human pathogen Corynebacterium resistens DSM 45100 isolated from blood samples of a leukemia patient.