What is a species complex?

What is a species complex?

Methods of classification of fungi have become highly sophisticated over the last decades. In taxonomy, species are described and rearranged almost exclusively by molecular techniques: sequence diversity of ribosomal genes, supplemented with differences in more variable secondary barcoding genes, and eventually – optimally – correspondence with phenotypic characters. These methods are much more precise than good old microscopy. Within almost every classical species, a stunning diversity can be observed: see for example the plethora of genotypes in Histoplasma (Rodrigues et al. 2020).

Some of the lineages in the labyrinth of genotypes are now being recognized as species. When distinguishable only molecularly, we call them cryptic species, or molecular siblings. A genome comparison of Histoplasma led Sepulveda et al. (2017) to describe Histoplasma mississippiense, H. ohiense and H. suramericanum, in addition to H. capsulatum. Another common species, Aspergillus fumigatus, has A. fumigatiaffinis, A. fumisynnematus, A. lentulus, and A. thermomutatus as nearest neighbors (Wiederhold et al. 2018; dos Santos et al. 2020). This increased taxonomic precision is useful for epidemiology (Cmokova et al. 2020), and may underline different trends in virulence and predilection (Su et al. 2018) or antifungal susceptibility (Lamoth 2018).

However, practical diagnostics is often lagging behind. Most taxonomic papers demonstrate the validity of species with multilocus phylogenetic trees, but that is not very practical if you just want to identify a single strain in your lab. De Almeida et al. (2019) complained that the molecular siblings in Histoplasma were very difficult to identify, and Song et al. (2021) had similar problems in Fusarium. For the hospital, focused diagnostic methods are required, such as provided by Kaplan et al. (2021) to distinguish the Blastomyces gilchristii sibling from B. dermatitidis.

Besides, the clinical significance of the siblings is not always obvious at the moment of description of the species. Sometimes this becomes apparent when more (clinical) data become available, but such questions go beyond the daily demands of hospital routine. Intra-specific variation in relevant traits may be larger than differences between siblings (dos Santos et al. 2020). For this reason, the concept of species complex can be very useful. From this perspective, a species complex can be defined as a monophyletic group of cryptic species for which the clinical relevance has not yet been proven (Chen et al., 2016; Kwon-Chung et al., 2017). Species complexes are listed in the Atlas as ‘member of …. complex’ with the species name. Notably, as soon as (clinical) relevance has been proven, the species complex should no longer be used. This is for example the case in Sporothrix, where S. brasiliensis, S. globosa and S. schenckii differ in their prevalent route of infection, being either plant- or feline-transmitted (Zhang et al. 2015; della Terra et al. 2017). For publication, correct identification of each sibling is necessary. But in clinical routine, exact identification is not always required; time-consuming phylogenetic approaches may then be regarded as inappropriate use of healthcare funds. Also Aspergillus lentulus in the A. fumigatus complex is, despite variation, an important entity to recognize (Yu et al. 2020).

Dermatophytes are a special case. Gräser et al. (2006) described clonal lineages that emerged from sexually interacting groups of strains. The original lifecycle of a dermatophytes involves the production of beautiful sexual fruitbodies in the environment. On the human host, cells just reproduce clonally; such lineages were termed ‘clonal offshoots’. These are molecularly, and sometimes also phenotypically a bit different from each other. Dermatophyte species thus consist of clusters of clones, which may or may not interact with mating in nature. However, some of the offshoots can be clinically relevant. This is the case with a virulent, often terbinafine-resistant clone in the Trichophyton mentagrophytes complex (Singh et al. 2018). As it is clinically significant to recognize this offshoot, it has been named as Trichophyton indotineae. Note that there are more offshoots in the same species complex (Tang et al. 2021), but these don’t have a name because they are clinically irrelevant.

Thus in clinical practice, whether or not to use the name of a molecular sibling depends on your personal needs. Broadly speaking, using ‘complex’ brings us more or less back to species concepts in pre-molecular times, while ‘sibling’ is more advanced.


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