Oligella spp.: A systematic review on an uncommon urinary pathogen

Background Oligella is an uncommon Gram-negative coccobacillus that was first thought to belong to the urogenital tract. The genus Oligella comprises two species that were recovered from various samples worldwide. Methods We perform a systematic review focusing on Oligella microbiological characteristics, habitat, role in Human microbiome and infection, and antimicrobial susceptibility. Results In humans, Oligella is mainly found as part of the microbiome of individuals with predisposing conditions. Oligella were also associated with invasive infections in patients with underlying diseases. Nevertheless, their prevalence remains to determine. Oligella culture requires up to 48 h on agar media in vitro, while urinary samples are usually incubated for 24 h. Consequently, microbiologists should be prompt to prolong the incubation of agar media when the direct examination showed Gram-negative coccobacilli. Oligella is accurately identified using MALDI-TOF mass spectrometry, but biochemical methods often provided inconsistent results. Specific guidelines for antimicrobial susceptibility testing of Oligella lack but the incubation could require up to 48 h of incubation. In contrast to O. urethralis, which is susceptible to third-generation cephalosporin, O. ureolytica is likely resistant to numerous antimicrobials. Genectic determinants of resistance were identified for beta-lactams and aminoglycosides. Conclusion Oligella is an uncommon pathogen that can be underrecognized. Microbiologists should be prompt to prolong the incubation of agar media plated with urines when the direct examination showed Gram-negative coccobacilli. Carbapenems should probably be given for the empirical treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s10096-024-04797-9.


Introduction
An increasing number of bacterial genera and species were described since bacterial taxonomy is based on a molecular approach.Of them, the genus Oligella spp. was described in 1987 [1].While it was first thought to belong to the urogenital microbiota, the bacterium has been recovered from various samples.Indeed, Oligella spp. was sparsely associated with invasive infections in patients with underlying

Search strategy
Searches in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Statement (PRISMA) guidelines [5] were conducted in PubMed/Medline among studies published from inception to and including October 31, 2023.The following search strategy was used: (Oligella) OR (Moraxella urethralis) OR (CDC group IVe).

Inclusion and exclusion criteria
Case reports, case series, cohort studies, and clinical trials on Oligella spp.infections were eligible as well as all reports describing Oligella site of isolation, characters and antimicrobial susceptibility.Isolates with ambiguous identification (i.e.not reaching the criteria for accurate identification for the method) were excluded.Studies in languages other than English were not eligible.

Study selection
The author performed the literature search.Conforming to the PRISMA guidelines, firstly titles or abstracts were screened.Relevant publications were identified, the full text was read and assessment was based on the inclusion and exclusion criteria previously mentioned (Fig. 1).Using the eligibility criteria, EF and AV independently screened all articles and abstracts and reviewed the full text of potentially eligible abstracts.

Data extraction
The following data were extracted from each eligible article: socio-demographic characteristics, the bacterial species, the type of infection, predisposing conditions, associated micro-organisms, and outcome.Data relative to the site of isolation and the microbiological characters of the isolate (i.e.phenotypic biochemical, antimicrobial susceptibility) were also extracted.

Risk of Bias
To assess the quality of included studies, the Joanna Briggs Institute (JBI) critical appraisal checklist for case reports was performed [6].Risk of bias is shown in Supplemental File 1.

Taxonomy and microbiological characteristics
The genus Oligella belongs to the family Alcaligenaceae.It comprises two species, Oligella urethralis (formerly Moraxella urethralis) and Oligella ureolytica (formerly CDC group IVe) [1].The closest relatives are Taylorella equigenitalis and members of the family Alcaligenaceae.Nevertheless, the taxonomic position of Oligella was based on DNA-DNA hybridization or DNA-rRNA hybridization [1].A more recent approach based on whole genome sequencing would probably precise the taxonomic position of Oligella [7].

Identification
The performances of laboratory methods of identification were almost never assessed as part of specific studies.Nevertheless, some isolates from case reports were identified using one or more methods.Biochemical methods could provide incomplete or inconsistent identification.The API 32GN was reported once to provide identification to the genus level of an isolate of O. ureolytica [2].Using the Minitek system, O. urethralis was likely misidentified, whilst O. ureolytica is correctly identified with sometimes the need for additional tests [13].Yamaguchi et al. reported the precise identification of a clinical isolate of O. urethralis was difficult using the MicroScan Walkaway 96 Plus (Beckman Coulter).Conversely, some isolates of both species were identified using the Vitek systems (BioMérieux) with a high probability score [2,[14][15][16][17].Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) media with perforation [27].Furthermore, Using a 16 S rRNA gene sequencing, Oligella was also identified in the outer ear and middle ear swabs of indigenous Filipino children [28].Sixteen children were included in the study of which 11 carry the A2ML1 variants gene that is associated with otitis media susceptibility.Oligella spp. was detected in the outer and/or the middle ear of thirteen (81.3%) children [28].In this population, Oligella spp.relative abundance was higher than that of Corynebacterium spp [28].

Digestive microbiota
Relatedness of gut microbiota and subclinical carotid arterial atherosclerosis was assessed in a study including 569 asymptomatic elderly in rural China [29].Subclinical carotid arterial atherosclerosis was significantly associated with gut microbiota and lifestyles [29].Indeed, lifestyle and diet are associated with atherosclerosis and cardiovascular diseases [30][31][32].In Zhu et al. study, fecal metagenomic analysis revealed a down-regulating abundance of 3 bacterial genera, i.e.Oligella, Alistepes, and Prevotella, that was correlated to taking more fresh aquatic food, vegetables, fruits, and doing more exercise [29].The gut microbes explained 16.5% of the mediation effect of lifestyles on the pathogenesis of carotid atherosclerosis [29].
Using a model of high-fat diet-induced obesity of rats, banana-resistant starch was shown to reduce the abundance of 3 bacterial genera, Oligella, Turicibacter, and Romboutsia, and increased that of Bacteroides, Ruminococcaceae, and Lachnospiraceae [33].Whilst, supplementation of young rat food with compound polysaccharides significantly increased the abundance of 4 bacterial genera (Bifidobacterium, Lactobacillus, Allobaculum, and Oligella) and was associated with the development of the metabolic activity of intestinal microbiota [34].In another study, the impact of fecal microbiota on nephropathy induced by hyperuricemia was assessed using an experimental model of rats based on the administration of a large amount of urate precursors [35].The gut microbiota was significantly changed compared with the control group: Flavobacterium, Myroides, Corynebacterium, Alcaligenaceae, and Oligella increased significantly while Blautia and Roseburia were greatly reduced.

Urogenital microbiota
Urine is a low microbial biomass environment and its analysis requires specific technical considerations [36].Thus, sensitive extraction methods are required to obtain good quality DNA and detect low-abundant bacteria [36].The detection of Oligella spp.might in urine sample using a molecular approach might therefore depends on the method used.mass spectrometry performances were never assessed for Oligella species, but the identification of at least 2 isolates of O. urethralis using MALDI-TOF mass spectrometry was confirmed using 16 S rRNA gene sequencing [4,18].

Habitat
Oligella spp.has been recovered from a wide range of human, animal, and environmental samples worldwide (Table 2).Among a collection of 28 O. urethralis received by the American Center for Disease Control (CDC), 16 (57.1%)and 3 (10.8%)were from urine and genital samples respectively suggesting the bacteria is a commensal of the urogenital tract [11].Furthermore, Oligella urethralis was recovered from more than 10% of urine samples of 60 women with urgency urinary incontinence in the absence of clinical infection [19].
Oligella was also isolated from environmental sources and manufactured products.The U.S. Food and Drug Administration identified microbial contamination in 49% (42 over 85) of unopened tattoo and permanent makeup inks purchased in the U.S [20]. .Of the bacterial contaminant, Oligella ureolytica was recovered from one unopened tattoo ink [20].The pistol pump automated injection system used for the injection of contrast agent/saline solution for magnetic resonance imaging could be at risk of bacterial contamination.In Germany, bacterial contamination was assessed at 3.9% among 205 samples, of which O. ureolytica was recovered once [21].Oligella urethralis was also recovered from 1 (0.8%) of 131 bulk tank milk from dairy herds in eastern South Dakota and western Minnesota [22].Oligella spp. was isolated from a water reservoir in Poland [23].

Ear microbiota
Using a genomic approach based on 16 S rRNA gene sequencing, Taylor et al. assessed the microbiota of Australian aborigines with otitis media.Participants were 19 children having a median age of 3.2 years (extremes 3 months − 7 years) [27].Oligella spp. was found to be significantly more abundant in children having ear disease with perforation, detected in 16% of all ear swabs.Relative abundance reached up to 60% in a 2-years old child with acute otitis another infectious cause [39].Of note, Oligella ureolytica had been recovered from a single blood culture vials sampled in a 18-months old children with a diagnosis of pneumonia [43].He recovered despite being administered with inactive antimicrobials, which makes the authors assume the isolate was a contaminant [43].

Antimicrobial resistance
Antimicrobial susceptibility testing and interpretation were performed using a wide range of methods and guidelines (Table 4).As Oligella spp.are slow-growing organisms, incubation of antimicrobials susceptibility testing was reported to require 48 h of incubation [43].O. urethralis is intrinsically susceptible to penicillins, cephalosporins, and carbapenems.Nevertheless, resistant isolates were described.Strain COH-1 was described to harbor two chromosomal genes encoding β-lactamases: bla ABA−1 , an AmpC cephalosporinase gene from Acinetobacter baumannii, and bla CARB−8 [44].Since O. urethralis reference strains CIP102456, CIP116103, and CIP8133 did not harbor these genes confirm chromosomal integration in strain COH-1 [44].bla ABA−1 was subsequently renamed bla ADC−2 , the ADC class of β-lactamases was far described for Acinetobacter baumannii and Acinetobacter spp [45]. .Most strains of O. urethralis were rested resistant to fluoroquinolones while aminoglycosides and trimethoprim-sulfamethoxazole combination appeared active in vitro.
In contrast to O. urethralis, all strains of O. ureolytica display decreased susceptibility to ampicillin or amoxicillin suggesting O. ureolytica harbor a chromosomal encoding penicillinase gene.Some isolates were found susceptible to penicillin -penicillinase inhibitor combination.Thirdgeneration cephalosporins were active against a single strain of O. ureolytica [14], while all-but-one strains were susceptible to carbapenems in vitro.The single carbapenem-resistant strain was resistant to all β-lactams using the broth microdilution method with prolonged incubation time (48 h) [43].Imipenem and meropenem MIC were 8 mg/L and > 16 mg/L respectively.The mechanisms of resistance to β-lactams including carbapenems remain to be assessed for O. ureolytica.Fluoroquinolones, aminoglycosides, and trimethoprim-sulfamethoxazole showed inconsistent While Oligella was first thought to be commensal of the urogenital tract, a single study reports their place in urinary microbiota.Pearce et al. compare the female urinary microbiome in 60 women with urgency urinary incontinence in the absence of clinical infection in comparison to 58 women without urgency urinary incontinence [19].They found Oligella urethralis was only detected in the urine of women with urgency urinary incontinence.Overall, Oligella was cultured from more than 10% of the group with urgency urinary incontinence [19].

Conclusion
The genus Oligella comprises two species that were recovered from various samples worldwide.In humans, they are mainly found as part of the microbiome of individuals with predisposing conditions.But, Oligella were also recovered from environmental source and O. uretrhalis was isolated from animals.Oligella were mainly associated with invasive infections in patients with predisposing conditions.But their prevalence, including in urinary infections, remains to determine.Indeed, as they are uncommon, they are likely not reported in epidemiological studies.Their identification in the clinical laboratory is easy using MALDI-TOF mass spectrometry, but they could require up to 48 h to grow in vitro.Consequently, microbiologists should be prompt to prolong the incubation of agar media plated with urines when the direct examination showed Gram-negative coccobacilli.O. urethralis could acquire genes encoding antimicrobial resistance.O. urethralis is susceptible to third-generation cephalosporin.Conversely, O. ureolytica is likely highly resistant to antimicrobials.Carbapenems should probably be given for the empirical treatment.
However, since the bibliographic search mainly retrieved case reports and case cohorts, more studies with robust methodology including should be conducted to assess the prevalence of Oligella as a uropathogen.The factors associated with the risk of infection, and the mechanisms of resistance to antimicrobials remain to be clarified.

Table 1
Sample of origin of Oligella spp.strains

Table 2
Biochemical and cultural characteristics of O. urethralis and O. ureolytica

Table 4
Antimicrobial susceptibility of O. urethralis and O. ureolytica

Table 4 ( continued )
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