We thoroughly analyzed published literature concerning identification of Bartonella species in rats. For this review, we examine prevalence and diversity of Bartonella in rats belonging to the genus Rattus. Only in few instances, strictly for comparative purposes, we provided data on other mammalian species co-habiting with rats of Rattus. We conducted a literature search by various search engines, including PubMed, Scopus, BioOne, Medline, ScienceResearch, Google Scholar, OVID Medicine, and Web of Science. In the search, we used the following keywords: “Bartonella AND Rats,” “Bartonella AND Rodents,” “Bacteria AND Rattus,” “Rat-Borne Diseases,” “Rodent-Borne-Diseases,” “Urban Bacterial Diseases,” “Urban Rodents AND Pathogens,” and their combinations. We analyzed data from serological, molecular, and bacteriological detection of Bartonella in rats. Analyzing data obtained from different assays, we have given a priority to the results that included an identification of Bartonella species and genotypes.

Ecological factors, including size and structure of rat populations and animal movement patterns, may determine prevalence and species diversity of Bartonella in rats within urban territories (Firth et al., 2014; Himsworth et al., 2015; Peterson et al., 2017). During the survey conducted by Halliday et al. (2015) in Kibera, an urban slum in Nairobi, Kenya, the proportion of infected Rattus overall varied from 0 to 60% by trapping zone (Figure 2). In three zones (A, B, and D), Mus musculus was the dominant species and only four Bartonella isolates were identified in rats (Figure 2). Concurrently, in two other zones, Rattus rats dominated in rodent populations presenting 51% in zone C and 40% in zone E. In these two zones (C and E), several species of Bartonella were reported (Figure 2; Halliday et al., 2015).

According to the investigation conducted in New Orleans, Louisiana by Peterson et al. (2017), prevalence of Bartonella infections ranged from 0 to 97% of rats. Most Bartonella-positive rats (85%) were found within a single housing block of New Orleans. All Bartonella-positive R. norvegicus rats were captured at two locations, where no roof rats were present. Bartonella-infected R. rattus were captured from five locations. Though two species of rats (R. norvegicus and R. rattus) were found in four of these five locations, no R. norvegicus rats were Bartonella-positive there. A single Bartonella-positive R. rattus was captured at a location where R. norvegicus were absent. Of five trapping locations in New York City, Bartonella-positive R. norvegicus rats were reported in each of them; however, prevalence of infected rats at these locations ranged from 10 to 85% (Peterson et al., 2017).

Himsworth et al. (2015) demonstrated significant geographic clustering of Bartonella-positive rats within Vancouver, Canada. The prevalence of B. tribocorum varied significantly by city block, from 0 to 60.5%. Analyzing various ecological factors affecting prevalence of B. tribocorum in R. norvegicus rats from Vancouver, Rothenburger et al. (2018) noticed that the infection was significantly lower within city blocks with one or more low-rise apartment buildings compared to blocks with none. There was no significant association of the infection prevalence with rat abundance, suggesting a lack of density-dependent pathogen transmission. According to this analysis, the infection rate positively correlated with high minimum temperatures and the authors suggested that a baseline minimum temperature could be important for survival of fleas that serve are vectors for transmission of B. tribocorum among rats (Rothenburger et al., 2018).

Abreu-Yanes et al. (2018) defined environmental parameters related to the presence of Bartonella DNA in rats in the Canary Islands. Specifically, their data suggest that occurrence of Bartonella on islands of this archipelago is influenced by biological and climatic conditions that vary among the islands. The probability of Bartonella infection in rodents in La Palma Island was four times higher compared to Tenerife Island and no Bartonella-positive rats were found in Lanzarote Island. A study carried out by Vicente and Gómez López (2012) showed that the flea Stenoponia tripectinata seem to have some preference for the conditions found on the four western islands, which include both Tenerife and La Palma, whereas this flea species was found in none of the 157 rodents from Lanzarote that belongs to the eastern group of islands. The results suggest that the ecological conditions on the Lanzarote Island are not suitable for the development of fleas S. tripectinata, while the ecological conditions on the La Palma Island (the most northwestern island of the archipelago) are more favorable for completing the life cycle of these fleas, which likely provide transmission of Bartonella infection between rats (Vicente and Gómez López, 2012).

Although Bartonella infections are prevalent in urban rat populations around the world and in many cities and prevalence of the infection can reach very high rates, we noted that rats in some cities and villages were not infected with Bartonella or the infection prevalence was quite low. At least, such situations were reported outside of Asia where we have not found reports of Bartonella-free populations of rats when a sufficient number of animals was tested. One of the first thoughts to explain the absence of Bartonella in some rat populations leads to representation of a kind of “island syndrome” wherein some parasites were absent or rare when a new rat population is established by invasion of a small number of individuals. In the regions where rats of the genus Rattus rarely occupy certain urban habitats, such as in areas of Europe and North America, populations of city rats are well-separated, in fact resembling “island populations.” This can explain the absence of Bartonella infections in rats from many big cities of the continental United States.

Noticeably, rats from the coastal cities on both Atlantic and Pacific sides (Los Angeles, Baltimore, New Orleans, New York, and Vancouver) carried Bartonella, while populations of rats in non-coastal cities were Bartonella-free (Ellis et al., 1999). In spite of a large number of rats investigated in Yokohama, Japan (255 R. rattus and 84 R. norvegicus), all tested animals were Bartonella-negative (Inoue et al., 2008). The rats of both R. rattus and R. norvegicus were Bartonella-free from some zones of the city of Cotonou, Benin (Martin-Alonso et al., 2016.

We admit that these observations are limited for supporting this statement. We can only speculate that continuous arrival of new rats through seaports is a crucially important factor for circulation of Bartonella among rats. Assuming an “island effect” on the formation of Bartonella communities in urban rat populations, we have to consider factors contributing to isolation of rat populations, such as time of establishing rat populations, distance and connectivity between continental rat populations and seaports where arrival of new rats is more likely to occur, rat population size, etc. (Papkou et al., 2016).

The “island effect” is not the only plausible explanation for the absence of Bartonella in rat populations within some urban areas and in some situations might not be the most important. When Bartonella bacteria are introduced into a new territory with invasive rats, the local conditions might not be favorable for the long-term circulation of the parasites within the newly established host population. Continuing an analogy borrowed from population genetics, a situation leads to the so-called “bottleneck effect” when bacteria are likely to be subjected to extreme changes in a host population. A critical issue is an availability of factors required for continuous transmission of Bartonella bacteria between rat hosts. A presence of appropriate flea species, particularly, the Oriental rat flea (X. cheopis) that can act as vectors, and the level of flea infestation, would be especially important factors for survival of Bartonella in rats. Unfortunately, data on the distribution of fleas in urban rat populations in the U.S. are quite sparse.

The absence of Bartonella infections in Rattus rats in some Ugandan villages and overall low prevalence in invasive rats in northwestern Uganda (Billeter et al., 2014) present another interesting situation that contrasts with numerous studies demonstrating a high prevalence of bartonellae among Rattus rats in Asia and in many places outside of Asia, e.g., Nairobi City. The relatively low prevalence of the infection in rats in this part of Africa may relate to relatively recent introduction of Rattus rats into the West Nile region. This fact is in contrast to the well-established rat populations in the cities on the coastal parts of Kenya and Tanzania, which probably have existed for millennia because of the historical dispersal of humans and their cargo via ships (Aplin et al., 2011). Despite intensive investigations, only a single rat was reported on a boat moored at Rhino Camp on the west side of the Albert Nile in the late 1930s (Hopkins, 1949; Amatre et al., 2009). Despite “fairly intensive” trapping efforts at 11 sites on land in the West Nile and West Madi regions along the west side of the Albert Nile, no R. rattus were captured during a survey undertaken in 1937 and 1938 by Hopkins (1949). Indeed, R. rattus might not have become established in the West Nile until the 1950s or even the 1960s as this rat was first identified in 1958 in the Ituri District of the DR Congo, which lies across the border from the West Nile Region (Borchert et al., 2007). This is perhaps not surprising as Hopkins (1949) suggested that R. rattus was first introduced to Uganda in the early Twentieth Century, a date that agrees with Delany's belief that this rat species first appeared in the country around 1910 (Delany, 1975). In this part of Africa, outsiders were restricted and movement of crops was limited until 1914 when the region became a British protectorate (Borchert et al., 2007). This likely could restrict the relocation of R. rattus and thereby limit the introduction of Bartonella infected rats. The extension of the “Kenya and Uganda Railways and Harbors” to the western Uganda in 1956 or the construction of the bridge across the Albert Nile at Pakwach in 1969 could have lead to gradual spread of Rattus rats to Arua near the border with DR Congo.

Provided information suggests that rat-adapted Bartonella species originated from Asia. The first data supporting this claim came after collection of bacteria related to B. elizabethae in Rattus rats from three districts of Yunnan province of southwestern China (Ying et al., 2002). Following this report, multiple investigations of rats in Southeast Asia (Cambodia, Laos, Thailand, and Vietnam) have also confirmed ubiquitous distribution of this infection in native rat species of the genus Rattus (Bai et al., 2007, 2009; Angelakis et al., 2009; Jiyipong et al., 2012). In contrast to urban rats in many countries of the world where two rat species are observed, in Asia, various species of Rattus occupy natural habitats from tropical lowland to mountains. For instance, the ricefield rat (R. argentiventer) and the Malayan field rat (R. tiomanicus) are common in the rice fields and plantations and the Losea rat (R. losea) is more typical in gardens (Kosoy et al., 2015). At the same time, only few species of rats have evidently adapted to live closely to people; specifically, R. tanezumi rats are common in cities, small towns, and villages.

Overall, the prevalence of Bartonella infections was commonly high in rats in Asia, but not higher than in urban rats in Africa or Americas. For example, Jiyipong et al. (2012) reported Bartonella species in 9.6% of rats in Cambodia, 11.9% in Laos, and 11.0% in Thailand, all of which are lower than the rates reported in Los Angeles, U.S. (56%) or in Nairobi, Kenya (57%). While rats of various species of Rattus carried Bartonella in natural habitats in Asia, prevalence varied between species. For example, prevalence of infected individuals has significantly varied from 3.2% in R. exulans to 86.4% in R. norvegicus in Thailand (Bai et al., 2009) or from 10% of the R. rattus to 66.7% of the R. losea in Taiwan (Hsieh et al., 2010).

The most striking difference in Bartonella infection between aboriginal and invasive rats was in observed diversity of the bacteria. Bartonella bacteria found in urban rats in Africa, Europe, and North and South Americas belonged to one or a few species or genotypes; for example, all 102 infected rats from Vancouver, Canada carried bacteria identical to each other by the gltA, which is a quite sensitive genetic marker (Himsworth et al., 2015). The diversity of Bartonella strains found in rats inhabiting natural environments in Asia was very high. Investigating rats from 17 provinces in Thailand, Bai et al. (2009) identified 23 genetic variants, which clustered with not only B. coopersplainensis, B. elizabethae, B. phoceensis, B. rattimassiliensis, and B. tribocorum, but also with numerous Bartonella genotypes in intermediate positions between described species or were quite different from all known species. A novel genotype of Bartonella with the proposed name as “Candidatus Bartonella thailandensis” was identified in rats of Rattus surifer from Surin, a Thai province neighboring Cambodia (Saisongkorh et al., 2009). Klangthong et al. (2015) classified DNA sequences obtained from rats in Thailand into eight different cladograms. Bartonella sequences obtained from rats of several Rattus species from Southeast Asia represented over 40 different genetic variants and clustered into nine lineages (Jiyipong et al., 2012). All described rat-adapted Bartonella species were identified in rats (R. argentiventer, R. tanezumi, R. norvegicus, and Bandicota indica) from the Mekong Delta in Vietnam (Loan et al., 2015). The prevalence of Bartonella infection among rats trapped in farms, filed, and forest was 22.4%, much higher than the infection prevalence in rats that were purchased in city markets (8.7%). The highest prevalence was found in R. tanezumi (49.2%), followed by R. norvegicus (20.7%). No Bartonella was found in R. exulans. The species isolated from these rats were B. rattimassiliensis, B. tribocorum, B. elisabethae, B. coopersplainensis, and B. queenslandensis (corresponding to 43.8, 21.9, 18.8, 9.4, and 6.3% of 32 Bartonella-infected rats. Two species (B. rattimassiliensis and B. coopersplainensis) were identified in R. tanezumi only, while all other species of Bartonella were detected at least in two rat species (Loan et al., 2015). The prevalence of Bartonella species in rats from rural parts of Vietnam (Mekong Delta) was significantly lower than in Saigon Port, but the diversity of the species was evidently higher.

A comparison of Bartonella bacterial communities between aboriginal and invasive rats of the genus Rattus allows an investigation of the roles played by rats as carriers of these bacteria comparing the diversity of Bartonella genotypes in rats between Southeast Asia where presumably original diversification happened and other parts of the world where only two rat species were relatively recently introduced. Hayman et al. (2013) analyzed variations of one genetic locus (the gltA as the most widely used molecular marker for differentiation of Bartonella species) of 191 strains of rat-associated bartonellae from 17 countries. The phylogeographic analysis supported the hypotheses that Bartonella species likely originated in Southeast Asia. The analysis has also highlighted the role of R. rattus in disseminating Bartonella bacteria to other continents. Black rats have invaded most countries of the world with main introductions that happened through several commensalism events (Aplin et al., 2011). Furthermore, the phylogenetic analysis conducted by Hayman et al. (2013) demonstrated that diversification of species belonging to the B. elizabethae species complex occurred in Southeast Asia before some of the species belonging to this complex were transmitted to other geographic regions. Importantly, their analysis suggests that there were multiple disseminations of these bacteria within Asia and numerous introductions from Asia to other parts of the world. This conclusion is based on identification of several major clades of Bartonella strains of Southeast Asian origin that dispersed globally.

Specifically, Bartonella strains obtained from rats of the genus Rattus from different continents and countries were grouped into six major clades that presumably originated in Southeast Asia. Of those, one clade (A) is distributed globally with strains found in most regions, but not in Central Africa. Likely, R. norvegicus play the leading role in distributing Bartonella species belonging to this clade. The analysis also suggests that the process of bacterial dispersal in this species clade is still continuous. Strains belonging to another clade (B) were detected only in Asia and Western Europe. The strains belonging to the third clade (C) dispersed to countries of Africa, North and South America. Strains grouped into the D are found in Africa and North America, besides Asia. Clade E has limited geographic spread, with only a Eurasian distribution. Finally, the strains combined into the clade F are distributed across Pacific and were detected in East Asia, Australia, and western part of North America (Hayman et al., 2013).

Multiple field observations and limited experimental studies support the major role of rat fleas in transmission of bartonellae among rats. Gutiérrez et al. (2015) highlighted the importance of the level of the flea's host specificity, flea exchange between rodents, and flea abundance for success of transmission of Bartonella bacteria. The host specificity of some flea species, e.g., X. cheopis, may influence the acquisition or the restriction of specific Bartonella species and strains to rats. There are many reports of the presence of Bartonella DNA in ectoparasites collected from Rattus rats. Bartonella DNA was detected in 59.1% of 193 Xenopsylla cheopis fleas collected from 62 Rattus rats (R. exulans, R. norvegicus, and R. rattus) captured in Khon Kaen, the northeastern province of Thailand. Sequence analysis of DNA present in rat fleas from this area demonstrated the presence of Bartonella species similar to B. elizabethae, B. rattimassiliensis, B. rochalimae, and B. tribocorum (Billeter et al., 2013). Another study in Thailand targeting rats and their ectoparasites in villages from all regions of the country indicated that the prevalence of Bartonella DNA varied substantially depending on ectoparasite species (Klangthong et al., 2015). Of the multiple arthropods screened during this study, the highest prevalence of Bartonella DNA was in louse (Polyplax and Hoplopleura, 57.1%) and flea (X. cheopis, 25.8%) pools. Only few positive samples were found in pools of mites (Leptotrombidium and Ascoschoengastia, prevalence 1.7%) and ticks (Haemaphysalis species, prevalence 3.5%). Most identified sequences found in arthropods have been found in rats and belong to the B. elizabethae species complex. Eight sequences of B. tribocorum were detected from six flea pools. One genotype identified as B. queenslandensis (99.6% identity) was found in a flea pool. One flea pool was positive for Bartonella with genotype being not reported in rats, but still closely related to B. tribocorum (96.8 % identity). Some identified Bartonella sequences from tick and louse pools shared close similarity with B. coopersplainsensis. Interestingly, B. phoceensis DNA was detected solely from ectoparasites (louse, mite, and tick pools) (Klangthong et al., 2015). Fleas obtained from rats in Taiwan harbored DNA of several Bartonella species (Tsai et al., 2010). Bartonella DNA detected in eight lice (Polyplax) obtained from five Bartonella-positive R. norvegicus from Taiwan was identified as B. phoceensis. The authors noticed that fleas collected from adult rats (77.1%) more likely Bartonella-positive than fleas collected from juvenile rats (42.3%).

Laudisoit et al. (2014) reported a high prevalence of Bartonella DNA in rat fleas from Kisangani, D. R. Congo. Bartonella genotypes detected pools of fleas X. cheopis, ticks R. sanguineus, and mites Haemolaelaps from Nigeria were identical or similar B. elizabethae (97–100% similarity), but a genotype found in a flea Ctenophthalmus pool was B. tribocorum (97% similarity) (Kamani et al., 2013). Nine of 12 genetic variants detected in rat fleas in Uganda belonged to the B. elizabethae species complex (Bai et al., 2017). In Madagascar, B. elizabethae was found in fleas of Synopsyllus fonquerniei and X. cheopis, while B. phoceensis and B. rattimassiliensis were found in sucking lice of the genus Polyplax (Brook et al., 2017).

In New York City, Bartonella DNA recovered from Oriental rat fleas collected from Norway rats belonged to three Bartonella species. The most common sequences clustered with B. tribocorum, while sequences related to B. elizabethae and B. rochalimae were less common in fleas (Frye et al., 2015). There are more reports of Bartonella DNA detected in rat blood. The main message that we can deliver from these studies is that the range of Bartonella genotypes found in ectoparasites, especially in fleas matches very much the spectrum of bacterial species found in rats. This contrasts with some observations made during investigations of sylvatic rodent communities when a considerable discordance between genotypes of Bartonella obtained from several ‘rodent host-ectoparasite’ pairs was reported (Abbot et al., 2007). A recent experimental study conducted by McKee et al. (2018) supported vector capacity of Oriental rat fleas (X. cheopis) for transmission of a rat-adapted Bartonella species. Specifically, this experiment demonstrated acquisition of B. elizabethae by experimentally exposed rat fleas and excretion of Bartonella DNA in flea feces over several days (McKee et al., 2018).

Pathogens carried by Norway and black rats can lead to significant morbidity and mortality in people around the world (Himsworth et al., 2013). The first species of rat-associated Bartonella proven to be a human pathogen was B. elizabethae (at that time described as Rochalimaea elizabethae) (Daly et al., 1993). This bacterium was isolated from blood of a 31-year old male patient with endocarditis admitted to the Saint Elizabeth Hospital in Massachusetts, U.S. The patient had no history of exposure to cats or other pets or intravenous drug use. A source of the infection remained mysterious until Ellis et al. (1999) found relatively similar bacteria in rats from the U.S. Ying et al. (2002) reported a variety of similar bacteria in rats in Southern China and, finally, an identical bacterium was found to be prevalent in rats from Vietnam (Loan et al., 2015). Later, an identical bacterium was identified in a febrile patient in Bangladesh (Faruque et al., 2017).

The strains identical or closely similar to rat-adapted Bartonella species, including B. elizabethae, B. tribocorum, and B. rattimassiliensis were identified in blood clots from eight febrile patients from two Thai provinces, Chiang Rai and Khon Kaen (Kosoy et al., 2010). These genotypes represented more than one-half of the Bartonella genotypes identified in human patients with fever of unknown etiology enrolled into this study. Importantly, some genotypes identified in rats from Los Angeles showed 98.8% similarity to the isolate obtained from a Thai patient (GenBank accession number GQ225706) (Gundi et al., 2012). Moreover, the strain of B. tribocorum identified in a Thai patient was identical to a Bartonella sequence detected in X. cheopis fleas collected from R. norvegicus rats in Los Angeles, California (Billeter et al., 2011). More recently, a strain of B. tribocorum was cultured with a bacteremia level of 60 colonies per 1ml from the blood of a 64-year old male patient with complaints of fatigue, muscle pain, and headache in France (Vayssier-Taussat et al., 2016).

Another species of Bartonella (B. rochalimae), though not specific for rats, was found in Rattus rats and their fleas from Asia and America (Billeter et al., 2011; Gundi et al., 2012). This bacterium was originally described as a human pathogen when it apparently caused fever and splenomegaly in a U.S. patient who became ill after traveling to Peru (Eremeeva et al., 2007). This bacterium was found in dogs and many wild mammalian species (foxes, rats, shrews, gerbils, and raccoons), suggesting that multiple reservoirs may be involved in its maintenance (Bai et al., 2016).

From our standpoint, the most intriguing and convincing case was reported from Tbilisi, the capital of the country of Georgia, where an 18-year old woman was admitted to hospital with a 2-week history of malaise, fever, and severe lymphadenopathy (Kandelaki et al., 2016). The patient lived in a residential area within Tbilisi and had not recently traveled outside the city. Based on lymphadenopathy and some other clinical manifestations, clinicians suspected cat scratch disease (CSD) although the patient denied any contact with cats. The clinical specimens were sent to the laboratory and results proved that indeed the bacterium found in samples from the patient belonged to the genus Bartonella. However, analyses that are more precise demonstrated that the strain was not B. henselae, the agent of CSD, but belonged to the B. elizabethae species complex. Thorough phylogenetic analysis involving seven molecular targets demonstrated that the bacterium had a divergence of 3.4% from B. elizabethae and 5.6% from B. tribocorum. Most importantly, this strain was identical to the Tel Aviv strain of Bartonella, which is prevalent and the only strain identified among R. rattus rats captured in Tel Aviv, Israel (Harrus et al., 2009).

The results of several serological surveys supported a potential exposure of people to rat-adapted Bartonella species. A survey of 630 drug users conducted in Baltimore, Maryland, reported seroprevalence of antibodies to rat-specific B. elizabethae (33%), 3-fold higher than prevalence to the cat-specific B. henselae (11%) or louse-transmitted B. quintana (10%) (Comer et al., 1996). A similar survey conducted in Central and East Harlem in New York City showed an even higher prevalence of seroreactivity to B. elizabethae (46%) compared to antibody positivity observed to B. henselae (10%) and B. quintana (2%) (Comer et al., 2001). A study of homeless people in Stockholm, Sweden reported high seroprevalence (52%) to B. elizabethae (Ehrenborg et al., 2008). McVea et al. (2018) reported exposure to rat-associated Bartonella species among intravenous drug users in an impoverished neighborhood of Vancouver, Canada. A retrospective serological survey of archived specimens indicated that Bartonella antibodies are prevalent among febrile patients in the Kathmandu Valley of Nepal (Myint et al., 2011). When 11 cases with high titers were compared to eight different Bartonella antigens, the highest titers (ranged from 1:256 to 1:2,048) reported in three patients were against the antigen of B. elizabethae.

A high diversity of Bartonella species and strains on the one side and association of specific Bartonella species with mammalian hosts on the other, in our case with rats of the genus Rattus, provide an opportunity for reconstructing the movement of these bacteria from the jungles of Southeast Asia to cities on all continents except for Antarctica. The studies of Bartonella strains associated with the rats of genera Rattus and Bandicota demonstrated that these bacteria cluster into a separate phylogenetic lineage (Heller et al., 1998; Ellis et al., 1999; Ying et al., 2002; Castle et al., 2004; Gundi et al., 2004, 2009). These Bartonella species likely originated in Southeast Asia and subsequently dispersed from Asia with Rattus rats because of human activity. Later these bacteria became common and widespread in urban and peridomestic environments around the world (Childs et al., 1999; Ellis et al., 1999).

We have to distinguish roles played by rats as hosts of Bartonella within the lands where they had originally diversified from rats that have been translocated in recent human history. Data supporting the hypothesis of the Old World origin of Rattus rat-associated Bartonella species include the widespread occurrence of genetically related isolates of Bartonella species in R. norvegicus from Portugal, the United States, and South America (Buffet et al., 2013). On the other hand, there is an evident difference between the Bartonella isolates obtained from rats and from indigenous rodents of America (Ellis et al., 1999). The first evidence Bartonella genotypes from Southeastern Asia being related to B. elizabethae came from identification of the high diversity of Bartonella in R. tanezumi rats in several cities of southern China and in lesser bandicoot rats (Bandicota bengalensis) and black rats (R. rattus) in Dhaka, Bangladesh (Ying et al., 2002; Bai et al., 2007). A few of the multitude of genotypes found in these rats were identical to sequences of cultures from Rattus rats found in France, Portugal, and the United States.

We propose to consider a “source-sink” ecological model developed in the field of population ecology of animals and plants (Pulliam, 1988) for comprehending the differences described earlier in this article. According to the original scheme, rat populations distributed across source habitats within the native range in Asia (“source”) are self-sustaining; while the rat populations introduced to other continents (“sink”) can be maintained continuously only by immigration of rats from natural habitats. Assuming the role of aboriginal rat populations as “sources” and the role of commensal rats in the continents where rats were introduced relatively recently as “sinks,” we can propose one more component for inclusion into this conceptual model. The assemblage of Bartonella strains in rats inhabiting big cities in Asia is commonly less diverse compared to populations of rats in native habitats and rural areas within the range of natural origin, but more diverse than in cities of other continents. These communities represent intermediate positions in the “source-sink” model. For example, the number of rat species in Bangkok, Ho Chi Minh City, Yangon, and others is restricted to only two commensal rat species common to urban areas in Africa, Americas, and Europe; but have a reduced diversity compared to communities observed in the forests or fields in Southeast Asia outside cities. The reduced number of rats in big Asian cities can explain the intermediate rate of Bartonella circulated within these rat populations. For example, the diversity of Bartonella species observed in rats from Dhaka, Bangladesh (Bai et al., 2007) was higher than in rats from cities in Americas and Europe (Gundi et al., 2012), but lower than in natural and agricultural settings in Thailand (Bai et al., 2009). Although all described Rattus rat-associated species of Bartonella have a worldwide distribution, the diversity of Bartonella genotypes in rats from natural habitats of southeastern Asia is much higher compared to a number of strains reported in all cities of the world outside Asia.

In a number of studies, Bartonella infection prevalence was higher in R. norvegicus compared to R. rattus (Ellis et al., 1999; Hsieh et al., 2010; Martin-Alonso et al., 2016). In some situations, this difference can be explained by the load of ectoparasites carried by these rats, but likely this is not the sole explanation. Brettschneider et al. (2012) noticed a similar effect and argued that more detailed biological research on Bartonella infections is needed to explain such observations. Based on comparative phylogeography of invasive rats in the United States, Lack et al. (2013) came to conclusion that rats of R. norvegicus may contribute to a greater diversity of pathogens from various international sources and spread them across the U.S. compared to R. rattus. Their premise is based the data suggesting that gene flow among populations was higher for the Norway rats compared to R. rattus (Lack et al., 2013). In addition, their analyses support their hypothesis that R. norvegicus rats invade both Atlantic and Pacific coasts of the U.S. and likely from different points of their origin (Lack et al., 2013). A comparison of Bartonella observed in both R. norvegicus and R. rattus in the US cities (Ellis et al., 1999) and phylogenetic analysis of Bartonella isolates conducted by Hayman et al. (2013) support this supposition.

Bartonella species, being a highly prevalent and extremely diverse group of bacteria, are excellent sentinel organisms for evaluating the transoceanic and intra-continental movement of the pathogens by rats of the genus Rattus. The analyses described in this article confirmed the role of human-mediated distribution of invasive rat species in dissemination of rat-adapted parasites. Intensive collections and characterization of the Bartonella strains recovered from Rattus rats allowed the demonstration of the global dissemination of such strains from Asia to Africa, Australia, Europe, and finally to the Americas. Phylogenetic analyses of rat-adapted strains represent an interesting model for investigating pathogen-host coevolution. The interesting question remains how introduction of specialized parasites introduced via invasive rodent hosts can alter parasite community dynamics. Finally, the accumulation of reports of human cases associated with rat-borne Bartonella species has increased concern about public health consequences of the global distribution of these bacteria and their introduction to urban centers.

MK and YB contributed conception and design of the study, organized the database, wrote the manuscript.