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 conditions or compromised immune systems [2, 3]. Nevertheless, clinical and microbiological data are sometimes partial in case reports and cases series. Consequently, due to the rarity of Oligella spp. infections, there are no standardized treatment guidelines. However, empirical therapy with antibiotics effective against Gram-negative bacteria, such as beta-lactams or fluoroquinolones, is often initiated until susceptibility results are available [4]. Treatment should be individualized based on the site of infection, severity, and susceptibility testing. In order to manage Oligella spp. infection an overview of its role in Human infections and its antimicrobial susceptibility is at least required.

We reviewed microbiological characteristics, habitat, place in the Human microbiome, role in infection, and antimicrobial susceptibility of the genus Oligella.

Methods

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.

Fig. 1
figure 1

PRISMA flow diagram

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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.

Results

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].

Oligella are aerobic, oxidase-positive, catalase-positive, non-fermentative Gram-negative coccobacilli [4, 8]. O. urethralis is non-motile while O. ureolytica is motile by means of long peritrichous flagella [1]. Cultural and biochemical characteristics of O. urethralis and O. ureolytica are listed in Table 1 [1, 9,10,11]. . Both species form millimetric, non-hemolytic, non-pigmented, colonies on Columbia agar supplemented with 5% horse blood or chocolate agar after 48 h of incubation at 35 °C in aerobic conditions [4]. Almost all strains cultivate on Mac Conkey agar. Some strains of O. urethralis are able to grow at 25 and 42 °C, while O. ureolytica does not grow at 42 °C [1, 9, 12]. Both species did not ferment sugar and are positive for nitrite reduction reaction, while indol, and gelatinase activities are negative. O. urethralis and O. ureolytica could be differentiated using the following characters: urease, nitrate reduction, and p-Hydroxybenzoate.

Table 1 Sample of origin of Oligella spp. strains
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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) 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].

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

In animals, O. urethralis was recovered from the external genitalia of 11.6% of 43 donkeys (Equus asinus) [24], ovarian hydrobursitis of a female camel (Camelus dromedaries) [15], urinary tract infection in dairy cattle [25], conjunctiva of rabbit (Oryctolagus cuniculus) [26]. O. ureolytica has never been isolated from animals to date.

Microbiome

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 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.

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].

Infections in human

We retrieved 14 infections involving Oligella spp (Table 3). The median age was 51 years old [extremes 0–88] and the male/female ratio was 1.8. O. urethralis and O. ureolytica were involved in 6 and 7 cases respectively, the remaining isolate was identified to the genus level. All-but-one infection involved Oligella spp. alone. Almost all patients had predisposing conditions. The types of infections were: 1 pulmonary abscess (O. urethralis) [4], 1 Urosepsis (O. urethralis) [18], 2 chronic ambulatory peritoneal dialysis peritonitis (O. urethralis) [12], 1 Knee septic arthritis (O. urethralis) [37], 1 lymph node infection (O. ureolytica) [3], and 7 primary bacteremia (1 and 6 due to O. urethralis and O. ureolytica respectively) [2, 14, 16, 17, 38,39,40]. Invasive infections could suggest Oligella spp. display some virulence factors that could contribute to dissemination in patients with comorbidities. In all cases of primary bacteremia, urine samples were negative in culture [2, 14, 16, 17, 38,39,40]. Nevertheless, Oligella spp. are slow-growing bacteria that could require at least two days of incubation [4], whilst urine samples handled in clinical laboratories are usually incubated for 24 h. Consequently, an urosepsis could not be excluded. Furthermore, rarely encountered micro-organisms such Oligella spp. are usually not reported in studies assessing the prevalence of micro-organisms in UTI [41], and non-invasive infections are likely not reported in the literature. Therefore, the prevalence of Oligella as a urinary tract pathogen remains unclear.

Table 3 Reported infections involving O. urethralis and O. ureolytica
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The outcome was available for 11 patients, 8 recovered with antimicrobials [2, 3, 14, 16,17,18, 37, 42], 2 dead from Oligella infection [4, 40], and the remaining one dead from 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].

Table 4 Antimicrobial susceptibility of O. urethralis and O. ureolytica
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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: blaABA−1, an AmpC cephalosporinase gene from Acinetobacter baumannii, and blaCARB−8 [44]. Since O. urethralis reference strains CIP102456, CIP116103, and CIP8133 did not harbor these genes confirm chromosomal integration in strain COH-1 [44]. blaABA−1 was subsequently renamed blaADC−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. Third-generation 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 activity in vitro against O. ureolytica. Resistance to aminoglycosides was mediated by an aminoglycosides acetyl-transferase gene (acc(6’)-Ib) in an isolate of O. ureolytica from the urinary tract of a children in Iraq [46].

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.