Microbial Taxonomy Revision: Enough Is Enough! Or Is It?

“When we're doing these identifications by genetic methods and genomic changes, they say, ‘Oh wait a minute. This organism is different than that. While they produce the same disease, they look exactly the same on the plate, they produce the same biochemical reactions, but they're different in [x], so they give it a new name. And eventually everybody in the world is going to have an organism named after him because, you know, the [x] wasn't where it was supposed to be. I mean Pseudomonas maltophilia…likes maltose, hard to kill, lives in water, not a good disease to have, not a good bug if you're compromised. Name was OK, so they changed it to Xanthomonas maltophilia. Perfect name. Slightly yellow colony (xantho); monas (rod); we’ve got a rod with a yellow colony that loves maltose. So, what do they do? They change the name to Stenotrophomonas maltophilia. If you break the name apart, steno is stenographer; tropho (tropism or gravitation towards); monas. So you have a rod that gravitates toward stenographers. Now if that isn’t the dumbest damn name I've ever heard of, I don't know what is. Pseudomonas pickettii? We just got people used to calling it Burkholderia pickettii. Lo and behold, somebody finds out there's one genomic gaggle gaggle out of order in pickettii and now it's got a name like Ralstonia. For some, it sounds like great Italian food. So, I've just gone totally nuts on this stuff and I quit using the genus names. So, I'll call the floor and I tell them they’ve got a pickettii; they’ve got a maltophilia; they’ve got a cepacia. I don't give a genus name anymore because they’re confusing the hell out of the doc; he doesn't know what Stenotrophomonas means, but he sure knows what maltophilia means. So, I think we have to stop this rampant name changing on the basis of, you know, one small gaggle gaggle complex. I think it’s stupid.” (1) The preceding passage, quoted from a published short biography of a prominent clinical and public health microbiologist, was uttered more than 20 years ago relative to introductory efforts in bacterial taxonomy revision within non-glucose-fermentative gram-negative bacilli. Since that time, the field of microbial taxonomy has exploded with the advent and refinement of molecular diagnostic techniques, genetic sequencing techniques that are becoming more commonplace in the clinical microbiology laboratory, not to mention fields such as bioinformatics and microbiome analysis. As a result, dozens of novel taxa, some of which are relevant to clinical medicine, are published on a monthly basis in peer-reviewed journals, with a healthy proportion of these gaining acceptance in a reference clearinghouse for published bacterial taxonomy. Moreover, contemporary investigations within the aforementioned disciplines also reveal potential discrepancies or novel findings that may call current taxon classification into question, eventually resulting in a taxonomic revision. The introductory quote (laced with levity) in this counterpoint serves as a baseline for a discussion of the potential pitfalls of overarching microbial taxonomy revision. To be clear, this author is not suggesting that either novel taxonomic designations or taxonomy revision is an unnecessary evil. Rather, benefits of taxonomy revision have even been elucidated in a previous editorial in this journal (2) and include an improved understanding of disease pathogenesis (3) and the procurement of clinically relevant antimicrobial susceptibility testing (4) using appropriate guidance from bodies such as the Clinical and Laboratory Standards Institute (CLSI). One tenet of antimicrobial susceptibility testing which experiences changes on a nearly annual basis involves β-lactam antimicrobial resistance testing and/or supplemental methods for coagulase-negative Staphylococcus spp. Prescribed methods are frequently associated with a specific taxon within this arbitrary classification (5). Other benefits are added here. First, advancements in bacterial taxonomy can provide insight to disease epidemiology. As one example, previous conventional wisdom ascribed the non-glucose–fermentative gram-negative bacillus Elizabethkingia meningoseptica to clinically significant infections such as meningitis in neonates and nosocomial bacteremia and pneumonia in adults with reportedly high morbidity and mortality. However, findings from Lau et al. (6) confirmed more contemporary observations that Elizabethkingia anophelis is the most prevalent and seemingly more virulent species among all species of the Elizabethkingia genus. Secondly, bacterial taxonomy revisions can clarify unusual isolate phenotypes that are observed in the laboratory. In recent publications, Corynebacterium diphtheriae has been subdivided into species and subspecies designations that include C. belfantii, C. rouxii, and C. diphtheriae subsp. lausannense (7–9) on the basis of differential nitrate reductase, iron uptake, tox genetic determinant, MALDI-TOF mass spectrometry, and average nucleotide identity laboratory studies, as well as clinical presentation. Yet those who are in the practice of proposing taxonomic revisions must be cognizant of potential ramifications on clinical and public health practice. Two scenarios will be discussed, with the first being the 2017 revision of Enterobacter aerogenes to Klebsiella aerogenes (10). The impetus for this revision seemed innocent enough: a former Klebsiella spp. designation being declared illegitimate—thus opening up an opportunity for an inter-genus taxon transfer. The problem lies in the potential for chromosomal AmpC β-lactamase induction within the re-named K. aerogenes. This potential is historically more associated with organisms of the Enterobacter genus, rather than those of the Klebsiella genus. Potential clinical consequences are illustrated in Table 1. Displayed within the Table are Midwest United States antibiogram data encompassing 711 isolates of K. pneumoniae, 124 isolates of K. aerogenes, and 243 isolates of Enterobacter cloacae complex. (Specific antibiogram profiles may vary on the basis of geography.) With respect to first- through third-generation cephem agents, as well as a monobactam agent and one β-lactam/β-lactamase inhibitor combination, K. aerogenes isolates may actually more closely resemble E. cloacae complex isolates from an in vitro perspective. This in vitro perspective is important because these data translate into final microbiology laboratory reports. Medical microbiologists express concern that a provider may focus simply on the word “Klebsiella” within the report and consider empiric treatment history for the more commonly observed K. pneumoniae when prescribing therapy. The medical microbiologist is trained to provide only clinically relevant information on final laboratory reports, in part, as a means of preventing unnecessary antimicrobial utilization. Scenarios involving K. aerogenes actually play in the opposite direction—medical microbiologists actually fear the “undertreatment” of these infections as a result of uncertainty linked to this taxonomic revision. Abridged antibiogram for clinically significant Klebsiella pneumoniae, Klebsiella aerogenes, and Enterobacter cloacae complex isolates generated by a Midwest United States microbiology laboratory in 2020 [data courtesy of E. Beck, Ph.D., D(ABMM)]. Utilization of CLSI M100 urine isolate-specific interpretive criteria. Abridged antibiogram for clinically significant Klebsiella pneumoniae, Klebsiella aerogenes, and Enterobacter cloacae complex isolates generated by a Midwest United States microbiology laboratory in 2020 [data courtesy of E. Beck, Ph.D., D(ABMM)]. Utilization of CLSI M100 urine isolate-specific interpretive criteria. Hördt et al. (11) analyzed more than 1000 draft genome sequences of class Alphaproteobacteria, a group of diverse gram-negative bacteria, to clarify taxonomic relationships. The authors commented that past taxonomic assignments had relied upon poorly resolved 16S rRNA genetic trees and limited phenotypic characteristics. One of the more relevant findings to the medical microbiologist was the reassignment of several Ochrobactrum spp. to Brucella spp., including the human isolate formerly known as Ochrobactrum anthropi. Medical microbiologists are already familiar with O. anthropi, as some commercial products have misidentified clinical isolates of Brucella melitensis as O. anthropi (12). Brucella spp. are not only notorious for their inherent pathogenicity, but also for their potential utilization in acts of bioterrorism and for their United States Code of Federal Regulations designation as an overlap select agent and toxin. Encounter of a select agent in clinical laboratory practice not only requires documented securing of the agent (as well as the clinical specimen from which it was derived) in the laboratory and safe transfer of the agent/specimen or on-site destruction of the agent/specimen, but also prompts notification of federal, state, and/or local public health authorities regarding such activities (13). It is the concern of the medical microbiologist that the new taxonomic designation of B. anthropi (an organism that can already be erroneously identified as a pathogenic Brucella spp.) may result in confusion regarding ancillary reporting practices and, at worst, unnecessary alarm and panic. Other revisions have appeared to be well intentioned but have yet to be appreciated throughout the clinical community. A reclassification of Borrelia spp. spirochetes in 2014 (14) transferred Lyme borreliosis agents to the novel genus Borreliella, while retaining relapsing fever agents within the Borrelia genus. This proposal has been the subject of multiple competing commentaries in the literature, with one group suggesting that an insufficient collection of organisms served as the basis for these studies (15). Analogous unfavorable responses have been documented for the recent reclassifications of the former Mycoplasma genus (16) and several former Mycobacterium spp. (17). Consider, for a minute, the revision paradigm from a pedagogic perspective. Medical microbiologists are responsible for the training of future medical and clinical microbiology professionals, be they pathology residents/fellows, infectious disease practitioners, medical laboratory scientists, medical students, infection control practitioners, or the like. Within just the past 5 years we now have a commonly encountered Klebsiella spp. (K. aerogenes) that exhibits motility, possesses the ornithine decarboxylase enzyme, and is resistant to cefazolin (10). Our Proteus spp. and Serratia spp. isolates are no longer in the same Enterobactericeae family as our Escherichia coli and K. pneumoniae (and even K. aerogenes!) isolates. Some of these agents are now members of novel families within a novel-constructed order Enterobacterales (18). (Luckily, susceptibility testing for these agents has not changed drastically, as CLSI has granted long-standing guidelines the table heading of Enterobacterales.) An emerging agent of sexually transmitted non-gonococcal, non-chlamydial urethritis is now Mycoplasmoides genitalium (16). “Cdiff” has even changed—to a Clostridioides genus designation (19). Go back a few more years, add the oxidase-positive gram-negative bacillus Plesiomonas spp. (20) that is now a member of the Enterobacteriaceae family (oops, order Enterobacterales), add the fact that we have gone from HACEK subacute bacterial endocarditis or human bite wound infection organisms to “AACEK” organisms with a pair of Aggregatibacter spp. revisions (21), and the collective student head is spinning. Medical microbiology can be difficult enough to learn from a student perspective; the degree of difficulty increases when preceptors may be forced to implement 2 sets of terminology when explaining a singular concept. So, what can be done? Some have suggested simply ignoring taxonomic designation revisions, a la Dr. Koontz (1), to facilitate effective clinical communication. If the medical microbiologist endorses this philosophy, how far does one go? Do we go back to reporting our E. coli isolates as Bacillus coli (the original designation of this gram-negative bacillus, as reported by Migula in 1895, though not validly published)? How about Morganella morganii as Proteus morganii (22)? For those of us who are not as seasoned, what about reporting our Moraxella catarrhalis isolates as Branhamella catarrhalis or Neisseria catarrhalis (23)? How about Enterococcus faecalis as Streptococcus faecalis (24)? This commentary has yet to touch on medical mycology. The aforementioned challenges relative to bacterial taxonomy are also relevant to medical mycology and accentuated, at times, by the debate between anamorph (asexual reproductive) vs teleomorph (sexual reproductive, when observed) designations of a fungus isolate. Teleomorph designations (Emericella spp., Wickerhamomyces anomalus, and Neocosmospora spp. as selected examples) have been advocated as the reportable result, despite the fact that a number of infectious clinical entities are based on the corresponding anamorph designation (aspergillosis, candidiasis, and fusariosis, respectively). Moreover, the teleomorph designations Nakaseomyces glabrata and Pichia kudriavzevii, despite illustrating clinically relevant antifungal susceptibility traits that distinguish these yeast from many Candida spp., are often communicated as the anamorphs Candida glabrata and Candida krusei, respectively. With the tremendous increase of new taxa, the practice of polite ignorance or indifference may not be the best option. The status of nebulosity for a novel or revised bacterial taxonomic designation is lost when that taxon is either published in the International Journal of Systematic and Evolutionary Microbiology as primary literature or accepted by that journal on a validation list. The aforementioned journal essentially serves as the communicative body for the International Committee on Systematics of Prokaryotes—the ultimate authority on bacterial nomenclature. The better course of action may hearken back to advice from that loving, tough-as-nails mother to an adolescent child: “Deal with it.” Frankly, medical microbiologists should be devoting time to devising means of effectively implementing nomenclature revisions into laboratory practice and communicating such knowledge to their practicing clinical, epidemiology, and public health partners. In terms of laboratory accreditation (for some), the College of American Pathologists has for several years employed a checklist item relative to laboratories incorporating “taxonomic changes that potentially affect the choice of appropriate antimicrobials to report and/or the interpretative breakpoints to use” (25). Microbial taxonomy compendia relative to human clinical specimens are published on a semi-regular basis (26, 27) to assist the medical microbiologist in becoming cognizant of taxonomic changes that may be of public health or clinical significance. CLSI has convened a Document Development Committee for the purpose of formally assisting diagnostic human and veterinary microbiology laboratories in the implementation of novel, revised, and relevant prokaryotic and mycotic species taxonomy into laboratory practice. Published recommendations will likely include provisos relative to effective communication channels (both verbal and written) with clinical partners. The science of microbial taxonomy is not going away any time soon. Medical microbiologists must take a proactive stance in the sense of accurate procurement of clinically relevant data and effective dissemination of findings with utmost clarity. All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved. Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest: E. Munson, Clinical and Laboratory Standards Institute Committee. E. Munson, Hologic, Inc. None declared. E. Munson, Hologic, Inc. None declared. None declared. None declared. E. Munson, travel support from Hologic, Inc.