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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 11  |  Issue : 3  |  Page : 303-308

Helping map the taxonomical position of the Nontuberculous Mycobacteria (NTM) in cystic fibrosis


Laboratory for Disinfection and Pathogen Elimination Studies, Northern Ireland Public Health Laboratory, Belfast City Hospital, Belfast, Northern Ireland, UK

Date of Submission20-May-2022
Date of Decision22-Jul-2022
Date of Acceptance02-Aug-2022
Date of Web Publication12-Sep-2022

Correspondence Address:
John Edmund Moore
Northern Ireland Public Health Laboratory, Belfast City Hospital, Belfast, BT9 7AD, Northern Ireland
UK
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmy.ijmy_120_22

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  Abstract 


Background: Nontuberculous mycobacteria (NTMs) have now emerged as important opportunistic bacterial pathogens, particularly among patients with cystic fibrosis (CF). The development of improved molecular technologies and bioinformatics and the adoption of whole-genome sequencing to more isolates have allowed for a reanalysis of the existing taxa within the genus Mycobacterium, resulting in the renaming of some existing NTM Mycobacterium species to three novel genera, viz., Mycolicibacterium gen. nov., Mycolicibacter gen. nov. and Mycobacteroides gen. nov. This has resulted in controversy, particularly within the clinical community, accompanied by a reluctance to adopt and employ these new bacterial names. Therefore, the aims of this study were (i) to identify NTM organisms associated with CF lung disease that have been reported previously in the published literature, (ii) to examine the realignment of NTM organisms previously described in CF within the revised new mycobacterial taxonomy and renaming, and (iii) to identify and explore online taxonomical tools to help educate clinical medicine about recent changes in NTM taxonomy. Methods: Three tasks were performed, namely (i) to identify NTM organisms previously associated with people with CF, (ii) to examine the extent and scope of the reclassification of CF-related NTM species affected by changes in recent taxonomy and nomenclature, and (iii) to identify and examine the educational utility of online taxonomical educational tools/software (LifeMap [http://lifemap.univ-lyon1.fr/]; National Center for Biotechnology Information [NCBI] Taxonomy browser [https://www.ncbi.nlm.nih. gov/guide/taxonomy/]; and List of Prokaryotic names with Standing in Nomenclature [LPSN] [https://lpsn.dsmz.de/]). Mycobacterium (Mycobacteroides) abscessus was selected as the species to evaluate the application of these tools. Results: Twenty-one NTM species have been reported that have been associated with CF lung disease. Of these, two have been reclassified into the Mycobacteroides genus, two into the Mycolicibacter genus, and seven into the Mycolicibacterium genus. LifeMap, NCBI Taxonomy browser, and LPSN offered interactive visual support to better understand the taxonomy and nomenclature of NTM organisms. Conclusion: We, therefore, advocate that clinical and scientific parties employ these online tools to gain a better insight into the familiarization and understanding of such evolving NTM classification, thereby aiding a better lexicon and communication among all stakeholders.

Keywords: Bacterial classification, cystic fibrosis, Mycobacterium abscessus, nomenclature, nontuberculous mycobacteria, taxonomy


How to cite this article:
Moore JE, Millar BC. Helping map the taxonomical position of the Nontuberculous Mycobacteria (NTM) in cystic fibrosis. Int J Mycobacteriol 2022;11:303-8

How to cite this URL:
Moore JE, Millar BC. Helping map the taxonomical position of the Nontuberculous Mycobacteria (NTM) in cystic fibrosis. Int J Mycobacteriol [serial online] 2022 [cited 2022 Sep 29];11:303-8. Available from: https://www.ijmyco.org/text.asp?2022/11/3/303/355919




  Introduction Top


Nontuberculous mycobacteria (NTMs) have now emerged as important opportunistic bacterial pathogens, particularly among immunocompromised hosts.[1],[2] Current estimates indicate that NTM-related infections now supersede disease associated with Mycobacterium tuberculosis (MTB),[3] which is estimated to cause 10 million new cases of tuberculosis every year.[4] NTM organisms are found primarily in the natural environment, particularly in soil and water sources. However, changing social demographic patterns of housing, use of water, movement of people, travel, and employment are all potential factors, which may influence the epidemiology of NTM-associated disease.[5] Clinically, these NTM organisms present several challenges including clinical and laboratory diagnosis, as well as a treatment dilemma, due to high levels of antimicrobial resistance. The increasing incidence of NTM-related disease has now become well established globally. Several factors have been associated with the etiology of the disease, including (i) an aging population, (ii) an increase in levels of immunosuppression due to increased employment of biologics, immunosuppressive therapies, and steroids, (iii) an increase in populations of immunocompromised individuals, including those with HIV and AIDS, (iv) macrolide antibiotic usage, and (v) medical tourism. Rivero-Lezcano et al. published a seminal review on the factors responsible for driving this increase in NTM clinical cases.[6]

In cystic fibrosis (CF), NTM disease has now emerged globally as a worrying problem, in terms of detection, treatment, and infection control. Detection by culture, especially with the slow-growing NTMs, can be confounded by the presence of other organisms cohabiting the CF airways, including Pseudomonas aeruginosa and Burkholderia cepacia complex organisms, which are able to grow more quickly than the NTM organisms and which can outcompete the NTMs, which may go undetected and enter an endless loop of sputum collection, attempted NTM isolation, overgrowth of NTM organisms present with rapid growing cohabiting flora, culminating in a clinical request for a repeat sputum culture.[7] Treatment can be compromised due to the high prevalence of antibiotic resistance within the NTM organisms,[8],[9],[10] and the presence of highly resistance organisms creates a challenge for successful infection control.[11]

In the US, of the 10,220 individuals who had a mycobacterial culture performed in 2020, 1019 (10.0%) had a mycobacterial species isolated one or more times, a decrease from 13.9% in 2019.[12] Notably, the relative proportion of Mycobacteroides abscessus isolated in 2020 was higher than reported more than a decade ago in a CF Foundation-supported multicenter prevalence study.[13] [Figure 1] shows that Mycobacterium avium complex organisms were the most commonly isolated NTM organisms, accounting for just over half (54%) of all NTM isolates identified, followed by M. abscessus/Mycobacterium chelonae (40%) and others (6%). Data Source US Cystic Fibrosis Foundation Registry.[12]
Figure 1: Distribution of NTM species isolated from CF patients in the US in 2020. NTM: Nontuberculous mycobacteria, CF: Cystic fibrosis

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The taxonomic lineage of the genus Mycobacterium is shown in [Figure 2]. As of July 2022, the List of Prokaryotic names with Standing in Nomenclature (LPSN) details that the number of child taxa with a validly published and correct name is 195; the number of child taxa with a validly published name, including synonyms is 209 and the total number of child taxa is 261.[14],[15],[16] The genus currently consists of 209 species, with a validly published name, including synonyms, constituting (i) the MTB complex consisting of MTB, Mycobacterium africanum, Mycobacterium bovis, Mycobacterium microti, and Mycobacterium canetti; (ii) Mycobacterium leprae and Mycobacterium lepromatosis; and (iii) the NTM. Sometimes, the NTMs are referred to as “environmental mycobacteria,” “atypical mycobacteria,” and “mycobacteria other than tuberculosis.” The development of improved molecular technologies and bioinformatics and the adoption of whole-genome sequencing to more isolates have allowed for a reanalysis of the existing taxa within the genus Mycobacterium. In 2018, Gupta et al.[17] proposed an amended genus, encompassing the “TuberculosisSimiae” clade, which includes the major mycobacterial human pathogens, and four novel genera, viz., Mycolicibacterium gen. nov., Mycolicibacter gen. nov., Mycolicibacillus gen. nov., and Mycobacteroides gen. nov., corresponding to the “FortuitumVaccae,” “Terrae,” “Triviale,” and “AbscessusChelonae” clades, respectively.[17]
Figure 2: Taxonomic lineage of Mycobacterium gordonae

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Until now, the language describing NTM species associated with CF lung pathology employed by clinical CF teams has followed the taxonomical nomenclature that was in place prior to Gupta et al.'s study of 2018.[17] However, the publication of this study detailing these revisions in taxonomy and nomenclature has resulted in controversy, particularly within the clinical community, accompanied by a reluctance to adopt and employ these new bacterial names.[18],[19] Irrespective of the arguments for and against these changes, the net effect of the discordance will be the divergence between those in the clinical community, who wish to employ the original bacterial names, prior to Gupta et al.' paper[17] and those, particularly within the scientific community who wish to move forward, embracing the new taxonony and bacterial nomenclature. Such divergence could therefore potentially lead to confusion regarding bacterial names, with potential consequences for naming errors within the clinical setting. It is, therefore, important to strive to strike a balance – a kind of “Bacterial Esperanto” that allows the successful understanding and communication between both parties. One means to achieve this is to examine and help with the understanding of these bacterial name changes, with particular reference to those NTM organisms found within CF.

Therefore, the aims of this study were (i) to identify NTM organisms associated with CF lung disease that have been reported previously in the published literature, (ii) to examine the re-alignment of NTM organisms previously described in CF within the revised new mycobacterial taxonomy and renaming, and (iii) to identify and explore online taxonomical tools to help educate clinical medicine about recent changes in NTM taxonomy.


  Methods Top


Description of nontuberculous mycobacteria organisms previously associated with people with cystic fibrosis

The search engine PubMed, available freely at https://PubMed.ncbi.nlm.nih.gov/, was examined to identify those species of NTM organisms, which have been previously associated with people with CF. PubMed is maintained by the National Center for Biotechnology Information (NCBI), at the US National Library of Medicine (NLM), located at the National Institutes of Health. The search terms “mycobacteri*” and “CF” were included as title search terms.

Examination of bacterial names affecting cystic fibrosis nontuberculous mycobacteria-related organisms

NTM organisms previously associated with CF from (i) above were cross-checked against the revised bacterial taxonomy and nomenclature, as defined by Gupta et al. and were reclassified according to the new taxonomy and nomenclature.[17]

Identification and examination of the educational utility of online taxonomical educational tools/software

Three online taxonomical educational tools/software were assessed, including (a) LifeMap – Exploring the entire tree of life,[20],[21] available freely at http://lifemap.univ-lyon1.fr/); (b) NCBI Taxonomy browser (available freely at https://www.ncbi.nlm.nih. gov/guide/taxonomy/); and (c) LPSN (available freely at https://lpsn.dsmz.de/).[15],[16] Mycobacterium (Mycobacteroides) abscessus was selected as the species to evaluate the application of these tools.


  Results Top


Description of nontuberculous mycobacteria organisms previously associated with people with cystic fibrosis

This search identified 268 publications, from which 21 NTM organisms were detailed, as shown in [Table 1].
Table 1: Original and revised taxonomy and nomenclature of nontuberculous mycobacteria organisms found in patients with cystic fibrosis

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Examination of bacterial names affecting cystic fibrosis nontuberculous mycobacteria-related organisms

The 21 NTM organisms were further examined using the taxonomy and nomenclature described by Gupta et al.[17] Each species was described in terms of clade, rapid/slow grower, and revised taxonomy and nomenclature. Of these, two were reclassified into the genus Mycobacteroides genus, two into the Mycolicibacter genus, and seven into the Mycolicibacterium genus.

Identification and examination of the educational utility of online taxonomical educational tools/software

  1. The taxonomic lineage of the genus Mycobacterium, as well as the three novel genera, namely Mycobacteroides, Mycolicibacter, and Mycolicibacterium, is shown in [Figure 3]a,[Figure 3]b,[Figure 3]c,[Figure 3]d,[Figure 3]e. LifeMap is an interactive tool to explore the whole NCBI Taxonomy, which allows interactive zooming and panning to expand/contract the taxonomic lineages/levels.[20] The tool also allows a bacterial name to be searched and the associated lineage displayed
  2. The taxonomic lineage of Mycobacteroides abscessus as displayed by NCBI Taxonomy browser is shown in [Figure 4]
  3. The taxonomic lineage of Mycobacteroides abscessus as displayed by LPSN (https://lpsn.dsmz.de/) [Figure 5].
Figure 3: Taxonomic lineage of the genus Mycobacterium, as well as the three novel genera, namely Mycobacteroides, Mycolicibacter, and Mycolicibacterium, as displayed by LifeMap (http://lifemap.univ-lyon1.fr/). (a) Superkingdom level, (b) the Terrabacteria group, (c) the phylum, Actinobacteria, (d) the family, Mycobacteriaceae, (e) the genus, Mycobacteroides

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Figure 4: Taxonomic lineage of Mycobacteroides abscessus as displayed by NCBI Taxonomy browser (https://www.ncbi.nlm.nih.gov/guide/taxonomy/). NCBI: National Center for Biotechnology Information

Click here to view
Figure 5: The taxonomic lineage of Mycobacteroides abscessus as displayed by LPSN (https://lpsn.dsmz.de/).[15],[16] LPSN: List of Prokaryotic names with Standing in Nomenclature

Click here to view



  Discussion Top


The aim of this study was to examine the ramifications of the recent changes in mycobacterial taxonomy and nomenclature,[17] with particular reference to the NTM organisms associated with lung infections in patients with CF. The overarching objective of any naming system should be that it should be understood by everyone and that names employed are easily communicated and understood by all scientific and clinical stakeholders. A situation has recently developed whereby the rules governing bacterial taxonomy and nomenclature have allowed the scientific reclassification of the historical genus, Mycobacterium, into four new genera, the new names which are largely unfamiliar to the clinical community. This has resulted in controversy, whereby advocates of using the historical genus name cite several factors for not employing the new taxonomic names, including confusion with clinicians and laboratories, as well as providing little to no benefit with respect to patient care. These advocates also cite the need to revise laboratory standard operating procedures and testing algorithms and training of laboratory staff and clinicians, as well as minimizing potential errors.[18],[19] While these points are well made, the scientific case and its acceptance is also valid. This has resulted in a relative stalemate between advocates for not changing the name and employment of the newly valid taxonomic name in scientific publications.

As a result, we have attempted to explore where the issues lie and to explore ways to help with the understanding of the taxonomical positioning and naming of these contested species, to help improve the communication and understanding between all parties, clinical and scientific.


  Conclusions Top


To aid and support all stakeholders with an interest in these, and to further support their understanding of the taxonomical issues, several online tools, including LifeMap, NCBI Taxonomy browser, and LPSN, offer interactive support to help the user better understand the taxonomy and nomenclature and we have attempted to show the functionality of these educational aids and how these tools add value in an understanding of these issues. We, therefore, advocate that clinical and scientific parties with an interest in NTM organisms in CF employ these online tools to gain a better insight into the familiarization and understanding of such evolving NTM classification, thereby aiding a better lexicon and communication among all stakeholders.

Limitations of the study

While this study has attempted to retrieve reports of all cases of NTM infection in patients with CF, there may be other cases of NTM infection that have been published elsewhere which have not been found and included in the study.

Ethical statement

This study did not require ethical approval as it did not involve any human or animal subjects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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