Change of Plans: Overview of Bacterial Taxonomy, Recent Changes of Medical Importance, and Potential Areas of Impact

Abstract

The process of bacterial nomenclature change has evolved in complexity over time and continues to be an iterative process that is not without challenges. The importance and feasibility of such changes vary among basic researchers, clinical microbiologists, and clinicians. In recent years, clinically relevant changes have been made across Gram-positive and Gram-negative organism groups, as well as the mycobacteria. Updated clinical laboratory accreditation requirements state that clinical laboratories must update their reporting practices in the case of clinically relevant nomenclature changes. These updates may significantly affect various sectors of health care, including antimicrobial stewardship, laboratory protocols, and infection prevention procedures and policies. While regularly updating bacterial nomenclature aims to improve the accuracy and consistency of our microbial language, the potential impact of such changes must be considered.

HISTORY AND PURPOSE OF NOMENCLATURE UPDATES IN MICROBIOLOGY

The current bacterial nomenclature landscape is complex and ever-changing with the introduction of advanced sequencing technologies and changes in how microorganisms are grouped and associated. Current nomenclature methodologies are rife with controversy and dispersed among different schools of thought, including clinical microbiologists, industrial and agricultural microbiologists, and taxonomists, who view the impact and value of such changes through different lenses [1, 2]. Ultimately, categorizing and naming microorganisms aims to provide an accurate language for communication between microbiology and clinical communities. Still, the need for standardization in nomenclature practices and acceptance poses unique challenges.

Modern bacterial nomenclature is rooted in the binomial system proposed by the 18th-century naturalist Carl Linnaeus, who established the concept of taxonomy based on a genus and species [3]. Initially, genus and species names were derived from visualized organism characteristics or the names of the individuals who first described or discovered the organism [3]. Later, after growing organisms from culture in the laboratory was well established, Bergey's first edition of Determinative Bacteriology systematically classified bacteria into hierarchies based on distinguishing phenotypic characteristics [1]. Although practical, phenotypic classification could not provide an evolutionary framework to elucidate organism relatedness, which led to an explosion of molecular and genetic testing methodologies aimed at improving the granularity of taxonomy and classification in the following years [1]. Today, techniques such as genomic sequencing drive taxonomic discovery and reclassification. While far more accurate from an evolutionary perspective, changes to bacterial nomenclature pose a challenge to clinical microbiology and infectious disease practice, as several existing classifications are tied to clinical and public health initiatives and guidelines [1].

NOMENCLATURE PROCESS

As microbiome research has evolved, so too has novel bacterial taxonomy [4]. This explosion in organism identification and classification has increased the need for studies demonstrating these organisms’ clinical significance, a knowledge imperative for clinical microbiology laboratories’ functionality. While there is no official bacterial taxonomy, approved names are regularly published in the International Journal of Systematic and Evolutionary Microbiology, which is the official publication of the International Code of Nomenclature of Prokaryotes, otherwise known as “the Code” [5]. The history of the Code is rooted in 1930s Paris, where at the First International Congress of Microbiology, it was proposed that bacteria and viruses should have their own code [1]. Today, the Code includes archaea and has removed viruses. Since the development of the Code, it has been responsible for regulating names given to prokaryotes. However, it is important to note that this is different from officially classifying prokaryotes, for which there is no official process [6]. The process for nomenclature revisions is complex. Since 1975, the Code has regulated nomenclature by indexing names in a centralized system and “validly publishing” them if they meet certain criteria. Once these criteria are met and the name is published, it is considered to have standing in nomenclature [6]. After this step, manufacturers of clinical microbiology identification systems may choose to update organism names in their databases. It is also important to note that while any validly published name has standing in the nomenclature, there is no overarching requirement that the name has to be used. The use of a new name is entirely dependent on the choice to use it by the microbiology community. In the case of clinical microbiology laboratories, this choice may be driven by standards set by accrediting agencies. For example, as of 2014, US and international laboratories accredited by the College of American Pathologists (CAP) must adopt bacterial nomenclature changes for clinically significant organisms per CAP checklist standard M.11375 [7].

The nomenclature change process is further complicated by the concept of “taxonomic freedom” [8]. The choice of a new name is determined by the authors of the nomenclature change proposal and is generally not subject to any review by the microbiology community except for that which occurs during the publication review process. Due to the lack of a wider review, the potential impact of the name change on the larger microbiological community is rarely considered. Once a name is validly published, the complex rules of the Code make it extremely difficult to change the name unless there is a significant taxonomic reason for doing so [5].

NOMENCLATURE UPDATE PROCESSES IN THE CLINICAL MICROBIOLOGY LABORATORY

The CAP, a major accreditation organization for clinical laboratories in the United States and internationally, requires that laboratories adopt the updated taxonomic changes for any organism when it may affect antimicrobial treatment or interpretive breakpoints from antimicrobial susceptibility testing [9]. Organizations such as the American Society for Microbiology work diligently to regularly review recent nomenclature changes or discoveries submitted to the International Journal of Systematic and Evolutionary Microbiology and summarize them within a clinical context for microbiology laboratories to use [7]. While maintaining a standardized and representative microbial language is important, nomenclature changes have impacts that ripple throughout clinical microbiology [10], infection prevention, clinical infectious disease practice, and antimicrobial stewardship.

Impact on Laboratory Processes and Procedures

Changes to microbial nomenclature may directly affect susceptibility test methods and the interpretation of susceptibility test results. A salient example of this is the various nomenclature changes of the organism now known as Aggregatibacter [11]. When the organism was reclassified from Actinobacillus actinomycetemcomitans to the genus Haemophilus in the 1980s, the Clinical and Laboratory Standards Institute (CLSI) modified susceptibility testing recommendations to reflect this. Guidelines for testing and interpretive criteria were available in the M100 guidance document, and the use of Haemophilus test medium was recommended for organism suspension and inoculation of disk diffusion or broth microdilution methods [11]. Furthermore, a broad range of antimicrobial interpretations was available in the CLSI M100 for this organism group. In 2006, the organism was reclassified again but this time to a novel genus presently known as Aggregatibacter. After this change, susceptibility testing recommendations were moved from the M100 document to the HACEK organism section of the CLSI M45 document. The recommended culture medium for broth microdilution was changed, and the antibiotics with relevant interpretive criteria available from CLSI were significantly reduced [11]. This example demonstrates some, but not all, of the moving parts involved with nomenclature changes in the clinical laboratory. At times, as in the example of Aggregatibacter, a bacterial nomenclature change may affect susceptibility test result reporting practices and the media type and methods used to perform the testing accurately [11, 12]. Ultimately, these changes may have unintended consequences on patient care.

In other cases, bacterial nomenclature changes may significantly affect processes and procedures associated with specimen handling or organism identification [13]. Providing organism names not only gives clinicians the information that they need to make early treatment decisions for their patients but also allows medical laboratory scientists to take appropriate precautions when working with an organism that is preliminarily identified as a special agent [13]. Existing laboratory protocols may require special handling of certain organisms (eg, specialized personal protective equipment, an appropriately equipped biosafety level laboratory); such is the case with organisms that are considered highly pathogenic and easily aerosolized, such as Brucella species [13–16]. Rapid communication of nomenclature changes to organisms in this category is essential to patient care and for updating laboratory procedures and ensuring the safety of laboratorians [11].

Impact on Antimicrobial Stewardship and Education

The Centers for Disease Control and Prevention (CDC) lists 7 core elements of hospital antibiotic stewardship programs: hospital leadership commitment, accountability, pharmacy expertise, action, tracking, reporting, and education [17]. Of these, tracking, reporting, and education are directly affected by bacterial nomenclature changes. Tracking and reporting, which rely heavily on laboratory data like those used to compile an antibiogram [18], are directly related to the laboratory's ability to update and communicate nomenclature changes rapidly and effectively. Furthermore, delays to amending organism reporting practices may be compounded by difficulties associated with successfully getting changes made within the laboratory information system and commercial ID/antimicrobial susceptibility testing systems used [19]. Additionally, stewardship-focused education initiatives may rely on knowledge of accepted bacterial nomenclature to inform about appropriate prescribing practices, infection control measures, and local epidemiology. When bacterial nomenclature changes are implemented, the potential impact and needs should be considered across disciplines, including the microbiology laboratory, stewardship team, and infection prevention team.

CONSIDERATIONS FOR IMPLEMENTING NOMENCLATURE CHANGES

Implementing nomenclature changes in the clinical microbiology laboratory is a complex process and must involve all key stakeholders who will be affected by the implementation, including antimicrobial stewardship and infection prevention teams, infectious disease clinicians, and information services/technology (Table 1). Laboratory reporting practices and downstream follow-up will depend on whether new nomenclature changes are adopted, and this ultimately depends on the anticipated clinical impact of the changes, infrastructure, and laboratory accreditation requirements [13]. If it is decided that nomenclature changes will be adopted, the clinical laboratory should work closely with the manufacturers of their identification and susceptibility test systems to understand how to incorporate any database changes or to better understand the limitations of identification or reporting on the systems with respect to the nomenclature changes. Additionally, the laboratory should work closely with its information technology department to understand interoperability across systems and the capacity to build reporting comments or alerts [13]. Changes to workflow must also be considered, particularly those that may directly affect laboratorian health and safety.

Multidisciplinary approaches should be used to help translate changes made in the laboratory to clinical practice. The clinical microbiology laboratory should work collaboratively with the antimicrobial stewardship team, infectious disease clinicians, and infection preventionists to provide guidance and education on the clinical application of nomenclature changes and how it relates to antimicrobial use and patient management (Table 1). These collaborative efforts may include interventions focused on education, tracking, reporting, and studying the feasibility and impact of nomenclature change implementation.

RECENT CHANGES OF MEDICAL IMPORTANCE

Clostridioides difficile

Clostridium difficile was reclassified as Clostridioides difficile in 2016 (Table 2). Genetic analyses demonstrated that the organism belongs to the family Peptostreptococcaceae, but the suggestion that the organism be filed under a new genus called Peptoclostridium was met with significant controversy based on the taxonomic argument that Peptoclostridium was too large to be a single genus [43]. Based on this argument, the new genus Clostridioides was proposed. Ultimately, the authors made the pragmatic choice of choosing a genus name that started with a C to ensure that the recognizable abbreviated name C difficile could still be used for health care reporting and commercial product labeling [44]. Without the substantial taxonomic argument of genus size used to challenge the proposal of the Peptoclostridium name change, the clinical impact of the name change would not have been taken into account and would have had far-reaching effects on the field of infectious diseases, clinical microbiology, and infection prevention.

Family Mycobacteriaceae

Like the order Enterobacterales, the family Mycobacteriaceae has undergone revision (Table 2). The genus contained >190 species of Mycobacterium. Many of the species within this genus are prominent human pathogens, such as M tuberculosis complex and M leprae. Several other environmental mycobacterial species, often referred to as nontuberculous mycobacteria, are known to cause a variety of syndromes, from mild respiratory disease to skin ulcerations to severe disseminated disease in patients who are immunocompromised. Improved treatment options for severe immunocompromising conditions (HIV, leukemia, lymphoma) and the use of advanced diagnostics (eg, MALDI-TOF) have greatly improved identification of mycobacterial species.

In 2018, Gupta and colleagues utilized a comprehensive genomics approach to analyze 150 Mycobacterium species genomes to understand their interrelationships. On the basis of their results, they proposed that the single genus Mycobacterium be split into 5 clades within the Mycobacteriaceae family. The type genus Mycobacterium remains, as well as the genera Mycolicbacter gen nov, Mycolicibacterium gen nov, Mycolicibacillus gen nov, and Mycobacteroides gen nov [45, 46].

While the novel genus names all are similar to Mycobacterium, it has been suggested that these changes may have negative impacts on patient care and lead to confusion or uncertainty about the significance of an isolate reported in a clinical culture—especially given the fact that cases of nontuberculous mycobacteria have risen substantially and many of these species produce similar clinical syndromes in certain at-risk patient groups (eg, persons living with HIV or patients with hematopoietic cell transplantation) [47].

Cutibacterium acnes

Propionibacterium acnes underwent taxonomic revision in 2016 to Cutibacterium acnes (Table 2). On the basis of whole genome sequencing analyses, scientists concluded that the Propionibacterium genus of bacteria was too diverse, including organisms commonly found in dairy products, human skin, and cattle rumen. They evaluated 162 publicly available genomes comprising strains representing the various species found within the genus Propionibacterium, and they proposed that the organisms in this genus be reclassified into 3 distinct genera: Acidipropionibacterium, Cutibacterium, and Pseudopropionibacterium [48]. Now, the Cutibacterium genus includes species that are predominantly isolated from human skin. There are 3 subspecies of C acnes that are validly recognized under the International Code of Nomenclature of Prokaryotes: C acnes subsp acnes, C acnes subsp defendens, and C acnes subsp elongatum [49].

The change in nomenclature to Cutibacterium seems to have been met with less resistance or hesitancy as compared with other changes. The CLSI amended its anaerobic antibiogram appendix, which appears in the M100 document to reflect the name change. Because anaerobic susceptibility testing is most often performed in reference laboratories, the impact of making changes in most clinical laboratories has likely not been felt as with other examples.

Falseniella ignava

In 1998, 2 strains of a previously unknown Gram-positive coccus were found to be closely related to, but distinct from, Facklamia hominis [33, 50, 51]. This led to the establishment of the novel species Falseniella ignava. Other species of Facklamia were subsequently described, though they have been identified infrequently in clinical specimens. Based on molecular analyses, these organisms were found to be genetically distinct from one another, requiring taxonomic revision given that the genus Facklamia was no longer monophyletic.

Mammaliicoccus sciuri and M lentus

In 2021, Staphylococcus sciuri and S lentus were reclassified into the novel genus Mammaliicoccus [34, 52]. These organisms are known commensal organisms in the microbiota of the skin and mucous membranes of several animal species, including humans. M sciuri and M lentus have been identified in case reports as causes of bacteremia, endocarditis, and peritonitis [36, 53, 54]. Previously, these organisms were the only Staphylococcus species to be positive for the presence of cytochrome oxidase per the modified oxidase test.

Klebsiella aerogenes

In 2017, the organism Enterobacter aerogenes was renamed Klebsiella aerogenes after whole genome sequencing demonstrated that the organism was more similar to Klebsiella than Enterobacter (Table 2) [38, 49]. Following this taxonomic change, a single-center study comparing clinical outcomes between patients who had bloodstream infections caused by E cloacae complex and K aerogenes demonstrated a significant difference in important outcomes. While the baseline clinical characteristics of patients were similar between groups, patients infected with K aerogenes had significantly more poor clinical outcomes than those with E cloacae complex infections [55]. This nomenclature change had a considerable impact on clinical laboratories and infectious disease clinicians due to the well-described inducible AmpC β-lactamase activity harbored by the genus Enterobacter [21]. This nomenclature change ignited concerns that clinicians would fail to recognize the inducible β-lactamase capability of K aerogenes and select inappropriate therapy, potentially negatively affecting patient care [19].

Pseudoescherichia vulneris

Pseudoescherichia vulneris was described as a novel species in 1982 and associated with human wounds [39]. DNA relatedness of this novel genus ranged from 6% to 39% similarity with other members of the Enterobacteriaceae. It was on the basis of biochemical testing that this organism was placed in the genus Escherichia. Following its initial description, this organism has been identified as a pathogen in cases of bacteremia and sepsis, peritonitis, meningitis. In 2017, phylogenetic core genome analysis and 16S rRNA sequence similarity done by Alnajar and Gupta supported the reclassification of several species of Enterobacteriaceae, including E vulneris [50, 56]. These findings led to the creation of the novel genus Pseudoescherichia and placement of E vulneris as the sole species currently in this genus.

Brucella anthropi

The taxonomic placement of Brucella anthropi has been widely debated. Strains such as Achromobacter species, Agrobacterium-like strains, Alcaligenes species, and the former CDC group Vd strains were examined. Based on G + C content and DNA-DNA hybridization studies, these strains were classified as the novel organism Ochrobactrum anthropi in 1988 [57]. Many of these isolates were recovered from a variety of clinical specimen types, such as blood, urine, sputum, and wounds. However, unlike other species of the genus Brucella, which are zoonotic pathogens and cause the disease brucellosis, B anthropi is an environmental organism widespread in nature. The analysis of >1000 genomes of Alphaproteobacteria by Hördt and colleagues in 2020, using a genome BLAST distance phylogeny approach, supported including Ochrobactrum within the genus Brucella [58].

From the clinical microbiology perspective, the addition of the free-living organism O anthropi into the genus Brucella has been met with extreme concern, though it was not felt to be a strong-enough argument to refrain from its inclusion in the same genus [58]. The organisms that cause brucellosis are highly pathogenic and transmissible. These characteristics make these obligate intracellular bacteria a problem for veterinarians, physicians, and laboratory scientists. B anthropi does not possess the same characteristics or virulence factors as B melitensis, B abortus, B suis, B canis, B ovis, B neotomae, B microti, B papionis, and B vulpis. Laboratory-acquired infections are important sources of transmission when specimens or cultures containing the organism are not handled with the proper biosafety precautions [59, 60].

Enterobacterales

Enterobacterales is an order of facultatively anaerobic Gram-negative bacilli in the class Gammaproteobacteria, containing some of the most frequently encountered pathogens in the clinical microbiology laboratory. The family Enterobacteriaceae was created with a single-type genus (Enterobacter); however, there have been numerous and sometimes contentious challenges regarding the legitimacy of the family name and type species [61]. Groundbreaking work by scientists at the CDC in the 1980s—including expanded biochemical testing and morphologic, culture, and other biochemical features, as well as percentage G + C content and DNA-DNA hybridization studies—led to a seminal article published in the Journal of Clinical Microbiology describing new bacterial species within the family Enterobacteriaceae [62].

More recently, in 2016 Adeolu and colleagues utilized whole genome sequencing to identify interrelationships within the order by using core genome phylogeny. Based on this work, the order Enterobacteriales—which was never validly published according to the Code—was divided into 7 families comprising distinct clades of related genera based on overall genome similarity, 4 multilocus sequence analysis proteins, and the identification of conserved signature insertion/deletions [63]. The revisions were as follows: the emended family Enterobacteriaceae (Enterobacter-Escherichia clade), Erwiniaceae fam nov (Erinia-Pantoea clade), Morganellaceae fam nov (Proteus-Xenorhabudus clade), Yersiniaceae fam nov (Yersinia-Serratia clade), Hafniaceae fam nov (Hafnia-Edwardsiella clade), Pectobacteriaceae fam nov (Pectobacterium-Dickeya clade), and Budviciaceae fam nov (Budvicia clade) (Table 3). The order Enterobacterales contains >250 species. Multiple genera that were not sequenced as part of this work were placed into one of the families based on 16S rRNA gene sequence analysis; Plesiomonas was not assigned to any of the families in the revisions and remains incertae sedis (Latin for “of uncertain placement”).

From a practical standpoint, revisions to the higher-order levels of taxonomy as previously discussed are not likely to have much impact on the identification and reporting of these organisms when identified in clinical cultures as laboratories typically report organisms at the level of genus and species.

Klebsiella quasipneumoniae

Klebsiella pneumoniae, a well-known and frequently encountered clinical pathogen, was previously subdivided into phylogenetic groups named KpI, KpII-a, KpII-b, and KpIII [64, 65]. To better evaluate the phylogeny of Klebsiella species, Brisse and colleagues conducted 16S rRNA gene sequencing and multilocus sequence analysis based on rpoB, fusA, gapA, gyrA, and leuS genes, biochemical characteristics, and average nucleotide identity. All strains evaluated shared >97% sequence similarity of the 16S rRNA gene. Sequencing of the rpoB gene and phylogenetic analysis indicated that KpII-a and KpIIb were sister groups that differed by only 11 nucleotides but were distinct from K pneumoniae. KpII-a and KpII-b strains shared an average nucleotide identity of 96.4%, but the average identity of both groups was <94% when compared with K pneumoniae and K variicola. On the basis of these studies, the authors proposed the name K quasipneumoniae subsp quasipneumoniae subsp nov and K quasipneumoniae subsp similipneumoniae subsp nov for strains KpII-a and KpII-b, respectively [42] (Table 2).

The exact prevalence of these novel species remains underestimated. The typical methods used in most clinical microbiology laboratories, whether through biochemical profiles or MALDI-TOF, have been shown to incorrectly identify these novel species as K pneumoniae [66].

CONCLUSIONS

Updates to bacterial nomenclature are important in creating a common language among those who work with the organisms. Still, such updates are not without challenges for clinical laboratories and treating clinicians. Therefore, it is imperative not only to keep up with accepted nomenclature updates but also to consider how these updates may affect processes across the health care spectrum. Communication and involvement of all microbiology and clinical stakeholders are essential to effectively implementing these changes and understanding their potential impact. Finally, multidisciplinary guidelines and best practices are needed to support streamlined implementation or clinically relevant nomenclature updates.

References

Author notes